Download Standard Treatment Guidelines and Essential Medicines List for

STANDARD TREATMENT GUIDELINES
AND
ESSENTIAL MEDICINES LIST
FOR
SOUTH AFRICA
HOSPITAL LEVEL
ADULTS
2015 EDITION
Copies may be obtained from:
The Directorate: Affordable Medicines
Private Bag X828
Pretoria
0001
OR
Department of Health Website: http://www.health.gov.za/edp.php
First printed 1998
Second edition 2006
Third edition 2012
Fourth edition 2015
ISBN: 978-1-920031-95-4
NOTE:
The information presented in these guidelines conforms to the current medical,
nursing and pharmaceutical practice. Contributors and editors cannot be held
responsible for errors, individual responses to drugs and other consequences.
© Copyright 2015, The National Department of Health.
Any part of this material may be reproduced, copied or adapted to meet local
needs, without permission from the Committee or the Department of Health,
provided that the parts reproduced are distributed free of charge or at no cost – not
for profit.
Suggested citation:
Republic of South Africa. Essential Drugs Programme. Hospital level
(Adults) Standard Treatment Guidelines and Essential Medicines
List. 4th ed. Republic of South Africa: National Department of Health;
2015.
Published and funded by:
The National Department of Health, Pretoria, South Africa
FOREWORD
It gives me great pleasure to present the Fourth Edition, of the Adult
Standard Treatment Guidelines (STGs) and Essential Medicines List (EML)
for Hospital Level care.
The system for the selection of essential medicines in the South African
public health sector is evolving as our country moves towards the
implementation of National Health Insurance. The National Department of
Health, through the National Drug Policy, remains committed to ensuring the
availability and accessibility of good quality essential medicines that are
effective, safe, and affordable and, the rational use thereof. The STGs and
EML remains an important tool in achieving this goal.
These guidelines are as a result of a rigorous evidence based peer review
process. Congratulations to the National Essential Medicines List and Adult
Expert Review Committees and external stakeholders on a successful
collaboration and revision. I commend their continued commitment to
healthcare provision in South Africa.
Access to previous editions of the Adult Hospital Level STGs and EML was
mainly paper-based. To strengthen access and implementation of the
revised publication, the guideline will be supported by the development of a
mobile application format. I believe that we should now leverage the
capabilities of technology to facilitate efficient, point-of-care access to up-todate medicine information.
Ensuring that guidelines become an integrated and useful part of health care
remains a challenge. Implementation of the revised edition of the STGs and
EML calls for cooperation between all sectors of health care providers.
It is the hope of the National Department of Health that the revised
guidelines will contribute towards greatly improved quality of care for our
citizens.
DR A MOTSOALEDI, MP
MINISTER OF HEALTH
DATE:
i
INTRODUCTION
Access to essential medicines is a fundamental component in ensuring equitable
health care to all South African citizens. The Standard Treatment Guidelines (STGs)
and Essential Medicines List (EML) provides a platform for equitable access to safe,
th
effective, and affordable treatment options. It is thus my honour to introduce the 4
Edition of the Adult Hospital Level STGs and EML.
Essential medicines are selected through the review of available clinical evidence,
considering efficacy, safety and affordability. The STGs provide guidance for the
rational use of these essential medicines.
New features have been incorporated into the revised Adult STGs and EML for
Hospital Level care. These include the level of evidence and supporting citations, new
algorithms and a warnings and cautions for medicine use reference. Additionally, the
revised edition of the STGs and EML will be available in mobile application format.
This is intended to improve accessibility to all healthcare professionals at all levels of
care, and allows health care professionals immediate access to up-to-date information
and decision support at their fingertips.
The extensive use of antimicrobials has resulted in drug resistance that threatens to
reverse the life-saving power of these medicines. The revised STGs and EML features
a quick antimicrobial reference appendix supporting the initiative of antimicrobial
stewardship. In addition, a more comprehensive care package for anaesthesiology,
pain and intensive care is included.
The revised publication is the culmination of many months of intensive review by the
National Essential Medicines List and Adult Expert Review Committees, as well as
collaboration and peer review from various internal and external stakeholders including
National Department of Health Programmes, Clinical Societies and Health Care
Professionals.
It is envisaged that the STGs and EML will undergo continuous improvement through
the contributions of users, and therefore users are encouraged to submit their
comments and suggestions to the National Department of Health.
I am confident that the revised guidelines will contribute towards promoting rational
medicine use, preventing the development of AMR and improving the quality and
safety of health care.
MS MP MATSOSO
DIRECTOR-GENERAL: HEALTH
DATE:
ii
ACKNOWLEDGEMENTS
We would like to convey our sincere gratitude and thanks to the Adult Expert
Review Committee for their passion, dedication, technical expertise and
commitment to this process. We thank you for sacrificing the time.
We also thank the various stakeholders (doctors, pharmacists, nurses,
dieticians, professional societies and other health care professionals) for
their comments and contributions with submission of appropriate evidence
and technical medicine reviews. Your willingness to participate in this peer
review consultative process was integral in producing this excellent edition.
We look forward to continuous constructive engagement.
In particular, we would like to thank:
 The Chairperson of the Adult Expert Review Committee, Prof Parrish,
for his tireless support, continued dedication and innovative ideas.
 The Vice Chairperson of the Adult Expert Review Committee, Prof
Blockman, for his commitment and contribution to the process.
 Prof Maartens for his technical and editorial support.
NATIONAL ESSENTIAL MEDICINES LIST COMMITTEE (2014–2015)
Mr GS Steel (Chairperson)
Prof L Bamford
Dr E Bera
Prof GPG Boon (resigned)
Prof H Brits
Dr N Dlamini
Prof M Freeman
Dr G Grobler
Prof PM Jeena
Dr S Joubert
Prof G Maartens
Mr HT Mphaka
Ms MNM Ntshangase
Prof AG Parrish
Dr Z Pinini
Dr G Reubenson
Dr W Seaketso
Prof BW van de Wal (resigned)
Ms K Jamaloodien
Dr F Benson
Prof M Blockman
Dr C Clark
Mr M Dheda
Mrs D du Plessis
Mr A Gray
Dr P Holele
Ms Y Johnson
Dr J Lamprecht (resigned)
Dr P Mntla
Dr L Mvusi
Ms M Ndwande
Dr L Pein
Ms R Reddy
Dr C Scott
Ms N Thipa
NATIONAL ESSENTIAL DRUGS LIST COMMITTEE (2015–current)
Prof G Maartens (Chairperson)
Dr F Benson
Prof M Blockman
Dr C Clark
Prof L Bamford
Dr E Bera
Prof H Brits
Mr M Dheda
iii
Dr N Dlamini
Prof M Freeman
Dr G Grobler
Prof PM Jeena
Dr S Joubert
Mr HT Mphaka
Ms MNM Ntshangase
Prof AG Parrish
Dr Z Pinini
Dr G Reubenson
Dr W Seaketso
Ms D du Plessis
Mr A Gray
Dr P Holele
Ms Y Johnson
Dr P Mntla (resigned)
Ms M Ndwande
Dr L Mvusi
Dr L Pein
Ms R Reddy
Dr C Scott
Ms N Thipa
ADULT EXPERT COMMITTEE
Prof AP Parrish (Chairperson)
Prof M Blockman (Vice Chairperson)
Prof PJ Commerford
Dr AME du Plessis
Prof G Lamacraft
Prof F Suleman
Dr AD Black
Dr R Coetzee
Dr MF Chughlay
Dr S Joubert
Dr N Nematswerani
Dr MFPC van Jaarsveld
CONSULTANTS AND MEDICINE REVIEW AUTHORS
Dr E Bera
Mr P Daames
Dr EH Decloedt
Dr I Ebrahim
Dr R Kularatne
Dr T Kredo
Dr R Lancaster
Ms T Leong
Dr M Makiwane
Prof M Mendelson
Prof J Moodley
Dr U Nqebele
Prof B Rayner
Dr M Reddy
Dr V Black
Dr B Daya
Dr PA de Wet
Dr T Kredo
Dr N Govender
Dr R Kularatne
Dr J Leigh Taylor
Prof G Maartens
Dr P Marwick
Dr J Miot
Dr M Nejthardt
Dr M Raff
Prof W Spearman
Ms L Zeihen
COMMENTS AND CONTRIBUTIONS
Dr MS Abdool-Gaffar
Dr S Adam
Dr P Alexandris
Dr F Amod
Dr E Ancker
Mr K Helena
Dr F Henning
Dr RE Hodgson
Dr N Horn
Dr K Hornby
iv
Dr M Osman
Dr AA Parker
Dr I Paruk
Dr F Pirie
Prof J Pretorius
Dr K Balme
Dr C Bamford
Dr D Barnard
Dr F Bassa
Prof E Bateman
Dr Z Bayat
Dr S Bechan
Ms Y Bekeur
Dr E Bera
Prof R Blaauw
Prof K Boffard
Dr J Bornman
Prof E Buch
Dr A Burger
Prof J Carr
Sr A Cruickshank
Dr J Dave
Dr H Dawood
Dr Daya
Dr E De Vries
Dr EH Decloedt
Mr D den Hollander
Ms L Deysel
Prof J Diedricks
Prof L Dreosti
Ms A Du Toit
Dr B Emmink
Dr J Espinaco
Dr C Faber
Dr Z Farina
Prof C Feldman
Mrs M Forgan
Dr R Freercks
Dr S French
Dr S Gebhardt
Dr LN Goldstein
Dr K Govender
Dr N Govender
Dr R Griesel
Dr D Hagemeister
Ms H Hayes
Prof B Jacobson
Dr S Jaikarun
Dr L Jenkins
Mr D Joiner
Dr R Kaswa
Dr K Keddy
Dr T Kemp
Dr H Khan
Prof W Kloeck
Dr E Klug
Prof C Koegelenberg
Prof M Levin
Prof N Levitt
Ms L Lifson
Prof BG Lindeque
Dr R Llewellyn
Prof Z Lockhat
Prof C Lundgren
Prof G Maartens
Dr S Maharaj
Dr J Mahlangu
Dr F Maleka
Prof AD Marais
Dr L Marais
Ms C Marks
Prof HP Meyer
Ms N Misra
Prof GM Mody
Dr P Monteiro
Prof J Moodley
Prof Y Moosa
Dr N Moran
Prof AA Motala
Prof Motswaledi
Prof D Muckart
Ms A Muller
Dr L Nel
Ms S Njokwe
Prof M Ntsekhe
Dr D O'Mahony
Prof E Oosthuizen
EDITORIAL
Prof G Maartens (Clinical editor)
Ms T Leong
v
Prof PJ Pretorius
Dr N Procter
Dr LB Profitt
Prof F Raal
Dr SR Ramphal
Prof G Richards
Dr C Roberts
Prof I Roberts
Dr L Robertson
Dr A Robins
Dr A Robinson
Prof JL Roos
Prof I Ross
Dr T Rossouw
Ms C Schubl
Dr E Scriba
Dr S Sewpersad
Dr Sigcu
Prof W Sinclair
Dr MGL Spruyt
Dr M Steenkamp
Dr N Stempels
Prof A Stulting
Dr C Sutton
Dr GE Thom
Dr A Thornton
Prof M Tikly
Dr B Tipping
Dr E Turton
Dr IS Ukpe
Dr A Van Aswegan
Dr D van der Merwe
Dr N Van Zyl Smit
Mrs C Vedalankar
Prof L Visser
Prof LA Wallis
Dr PF Wessels
Dr L Weich
Dr L Wilken
Ms K Wium
Dr T Yates
Assistance was provided by:
Dr AD Black
Prof M Blockman
Mrs MC Jones
Ms G Mkele
Dr J Riddin
Dr J Jugathpal
SECRETARIAT
Ms T Leong
Dr J Jugathpal
Mr N Khalo
Dr R Lancaster
Dr J Riddin
LOGISTICS
Mr M Molewa
Ms P Ngobese
Mr GS Steel
Cluster Manager: Sector Wide Procurement
vi
Mr P Daames
Dr M Reddy
Mr P Hajison
TABLE OF CONTENTS
Foreword
i
Introduction
ii
Acknowledgements
iii
Table of contents
vii
The Essential Medicines Concept
xix
How to use this book
xxi
A guide to patient education in chronic diseases
xxx
CHAPTER 1 - ALIMENTARY TRACT
1.1
Gastrointestinal disorders
1.1.1 Bowel preparations
1.1.2 Diverticulosis
1.1.3 Gastro-Oesophageal Reflux Disease (GORD)
1.1.4 Hiatus hernia
1.1.5 Inflammatory bowel disease
1.1.6 Pancreatitis, acute
1.1.7 Pancreatitis, chronic
1.1.8 Peptic ulcer
1.2
Hepatic disorders
1.2.1 Hepatitis, non-viral
1.2.2 Acute liver failure
1.2.3 Portal hypertension and cirrhosis
1.2.4 Hepatitis, viral
1.2.4.1
Hepatitis B, acute
1.2.4.2
Hepatitis B, chronic (non-HIV
coinfection)
1.2.4.3
Hepatitis B, chronic (HIV coinfection)
1.2.5 Liver abscess, pyogenic
1.2.6 Liver abscess, amoebic
1.2.7 Acute cholecystitis and acute cholangitis
1.3
Diarrhoea
1.3.1 Cholera
1.3.2 Acute inflammatory diarrhoea (dysentery)
1.3.3 Diarrhoea, acute non-inflammatory
1.3.4 Diarrhoea, antibiotic-associated
1.3.5 Amoebic dysentery
1.3.6 Giardiasis
1.3.7 Typhoid
1.3.8 Bacterial peritonitis
vii
1.1
1.1
1.1
1.1
1.2
1.3
1.3
1.3
1.4
1.5
1.7
1.7
1.8
1.9
1.10
1.10
1.11
1.13
1.13
1.14
1.14
1.15
1.15
1.15
1.16
1.17
1.17
1.18
1.18
1.18
TABLE OF CONTENTS
CHAPTER 2 - BLOOD AND BLOOD FORMING ORGANS
2.1
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
2.10
2.1
2.1
2.3
2.5
2.5
2.6
2.7
2.8
2.10
2.10
2.11
2.14
2.16
2.11
2.12
2.13
2.14
Anaemia
Anaemia, iron deficiency
Anaemia, megaloblastic
Anaemia, chronic disorder
Anaemia, haemolytic
Anaemia, aplastic
Anaemia, sickle cell
Febrile neutropenia
Myelodysplastic syndromes
Bleeding disorders
2.10.1 Haemophilia A and B, Von Willebrand disease
Immune Thrombocytopenia (ITP)
Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic
Syndrome (TTP-HUS)
Acquired coagulation defects
2.13.1 Disseminated Intravascular Coagulation (DIC)
Venous thrombo-embolism
CHAPTER 3 - CARDIOVASCULAR SYSTEM
3.1
Ischaemic heart disease and atherosclerosis, prevention
3.2
Acute coronary syndromes
3.2.1
ST Elevation Myocardial Infarction (STEMI)
3.2.2
Non-ST Elevation Myocardial Infarction (NSTEMI)
and Unstable Angina (UA)
3.2.3
Chronic management of STEMI/NSTEMI/UA
3.2.4
Angina pectoris, stable
3.2.5
Atherosclerotic peripheral arterial disease
3.3
Cardiac dysrhythmias
3.3.1
3.3.2
3.3.3
3.3.4
3.3.5
2.17
2.17
2.18
3.1
3.1
3.4
3.4
3.7
3.9
3.9
3.10
3.11
Narrow QRS complex (supraventricular)
tachydysrhythmias
3.3.1.1
Atrial fibrillation
3.3.1.2
Atrial flutter
3.3.1.3
AV junctional re-entry tachycardias
Wide QRS (ventricular) tachyarrhythmias
3.11
3.3.2.1
3.3.2.2
3.17
3.18
Regular wide QRS tachycardias
Sustained (> 30 Seconds) irregular
wide QRS tachycardias
3.3.2.3
Non-Sustained (< 30 Seconds)
irregular wide QRS tachycardias
3.3.2.4
Torsades de pointes ventricular
tachycardia (VT)
Heart block (second or third degree)
Sinus bradycardia
Sinus arrest
viii
3.12
3.15
3.15
3.17
3.18
3.19
3.20
3.21
3.21
TABLE OF CONTENTS
3.4
3.5
3.6
3.7
Congestive Cardiac Failure (CCF)
Endocarditis, infective
Hypertension
3.6.1 Hypertension, asymptomatic severe
3.6.2 Hypertensive urgency
3.6.3 Hypertensive crisis, hypertensive emergency
Rheumatic heart disease
3.21
3.24
3.27
3.32
3.32
3.33
3.34
CHAPTER 4 - DERMATOLOGY
4.1
Acne
4.2
Cellulitis and erysipelas
4.3
Impetigo
4.4
Furuncles and abscesses
4.5
Atopic eczema/ dermatitis
4.6
Erythema Multiforme, Stevens Johnson Syndrome, Toxic
Epidermal Necrolysis
4.7
Leg ulcers, complicated
4.8
Psoriasis
4.9
Urticaria
4.9.1
Papular urticaria
4.10 Fungal infections
4.11 Viral infections
4.11.1 Viral warts/anogenital warts
4.11.2 Shingles (Herpes zoster)
4.1
4.1
4.2
4.3
4.4
4.5
4.7
CHAPTER 6 - GYNAECOLOGY
5.1
Dysmenorrhoea
5.2
Uterine bleeding, abnormal
5.3
Pelvic Inflammatory Disease (PID)
5.4
Endometriosis
5.5
Amenorrhoea
5.6
Hirsutism and virilisation
5.7
Infertility
5.8
Miscarriage
5.8.1
Silent miscarriage or early fetal death
5.8.2
Incomplete miscarriage in the first trimester
5.8.3
Midtrimester miscarriage (from 13–22 weeks
gestation)
5.8.4
Septic miscarriage
5.8.5
Trophoblastic neoplasia (‘Hydatidiform mole’)
5.9
Termination of pregnancy (TOP)
st
5.9.1
Gestation, 1 trimester (< 13 weeks)
5.9.2
Gestation, second trimester (13 to 20 weeks)
5.10 Sexual assault
5.11 Urinary incontinence
5.12 Menopause and perimenopausal syndrome
5.1
5.1
5.1
5.3
5.5
5.5
5.6
5.6
5.7
5.7
5.8
5.8
ix
4.9
4.10
4.11
4.12
4.13
4.14
4.14
4.14
5.9
5.10
5.10
5.11
5.12
5.13
5.14
5.14
TABLE OF CONTENTS
CHAPTER 6 - OBSTETRICS
6.1
6.1
6.2
6.3
6.4
6.5
6.6
6.7
6.8
6.9
6.10
Anaemia in pregnancy
Diabetes mellitus in pregnancy
Heart disease in pregnancy
Hypertensive disorders in pregnancy
Severe pre-eclampsia and eclampsia
Chronic hypertension
HIV in pregnancy
Syphilis
Jaundice in pregnancy
Hyperemesis gravidarum
6.1
6.2
6.4
6.7
6.9
6.11
6.11
6.14
6.15
6.16
6.11
Preterm labour (PTL) and preterm prelabour rupture of
membranes (PPROM)
Suppression of labour for fetal distress
Labour induction
Labour pain, severe
Dehydration/ketosis in labour
Postpartum fever
Postpartum haemorrhage
The Rhesus-negative woman
Urinary tract infection (UTI) in pregnancy
6.19.1
Cystitis
6.19.2
Pyelonephritis, acute
6.16
6.12
6.13
6.14
6.15
6.16
6.17
6.18
6.19
CHAPTER 7 - NEPHROLOGICAL/UROLOGICAL DISORDERS
7.1
Nephrology section
7.1.1
Chronic kidney disease (CKD)
7.1.2
Glomerular disease and nephritic syndrome
7.1.3
Nephrotic syndrome
7.1.4
Acute kidney injury
7.1.5
Renal replacement therapy
7.2
Major electrolyte abnormalities
7.2.1
Hyperkalaemia
7.2.2
Hypokalaemia
7.2.3
Hypernatraemia
7.2.4
Hyponatraemia
7.3
Urology section
7.3.1
Haematuria
7.3.2
Urinary tract infection (UTI)
7.3.3
Recurrent UTI
7.3.4
Prostatitis
7.3.5
Benign Prostatic Hyperplasia
7.3.6
Overactive Bladder
7.3.7
Erectile dysfunction
7.3.8
Renal Calculi
x
6.18
6.18
6.20
6.21
6.21
6.22
6.23
6.24
6.24
6.24
7.1
7.1
7.1
7.6
7.7
7.8
7.9
7.9
7.9
7.10
7.11
7.11
7.14
7.14
7.15
7.17
7.18
7.18
7.19
7.19
7.2
TABLE OF CONTENTS
CHAPTER 8 - ENDOCRINE SYSTEM
8.1
8.1
8.2
8.3
8.4
8.5
8.1
8.1
8.3
8.4
8.4
8.6
8.9
8.11
8.11
8.13
8.6
8.7
8.8
8.9
8.10
8.11
8.12
8.13
8.14
8.15
8.16
8.17
8.18
Acromegaly
Adrenal insufficiency (Addison disease)
Androgen deficiency
Cushing syndrome
Diabetes mellitus
8.5.1
Type 2 diabetes mellitus
8.5.2
Type 1 diabetes mellitus
Diabetic emergencies
8.6.1
Hypoglycaemia
8.6.2
Diabetic ketoacidosis (DKA) and hyperosmolar
nonketotic diabetic coma (HONK)
Complications of diabetes
8.7.1
Diabetic neuropathies
8.7.2
Diabetic kidney disease
8.7.3
Diabetic foot ulcers
Dyslipidaemia
Hypercalcaemia, including primary hyperparathyroidism
Hypocalcaemia
Hypothyroidism
Osteoporosis
Osteomalacia/Rickets
Paget disease
Pituitary disorders
8.15.1
Prolactinoma
8.15.2
Anterior hypopituitarism
8.15.3
Diabetes insipidus (Posterior hypopituitarism)
Phaeochromocytoma
Primary aldosteronism
Hyperthyroidism
8.18.1
Graves’ hyperthyroidism
8.18.2
Toxic multinodular goiter
8.18.3
Single toxic nodules
8.18.4
Thyroiditis
8.18.5
Thyroid crisis
CHAPTER 9 - SYSTEMIC AND HEALTHCARE-ASSOCIATED
INFECTIONS
Antimicrobial Stewardship
9.1
Healthcare-associated infections
9.1.1
Intravascular catheter infections
9.1.2
Surgical wound infections
9.1.3
Hospital-acquired pneumonia (HAP)
9.1.4
Urinary tract infections, catheter associated
9.2
Adult vaccination
9.2.1
Rabies vaccination
xi
8.16
8.16
8.17
8.17
8.18
8.20
8.21
8.22
8.23
8.24
8.24
8.25
8.25
8.25
8.26
8.27
8.28
8.29
8.3
8.31
8.31
8.31
8.32
9.1
9.1
9.1
9.2
9.3
9.4
9.5
9.6
9.6
TABLE OF CONTENTS
9.3
9.4
9.5
9.6
9.7
9.8
9.9
9.10
9.11
Brucellosis
Haemorrhagic fever syndrome
Hydatid disease
Malaria
9.6.1
Malaria, non-severe
9.6.2
Malaria, severe
Tetanus
Tick bite fever
Enteric fever (typhoid)
Varicella (Chickenpox), complicated
Zoster (Shingles)
9.8
9.9
9.10
9.11
9.11
9.12
9.14
9.15
9.15
9.16
9.17
CHAPTER 10 – HIV AND AIDS
10.1 Antiretroviral therapy
10.1.1
HIV in kidney disease
10.1.2
Management of selected antiretroviral adverse
drug reactions
10.1.3
Immune reconstitution inflammatory syndrome
(IRIS)
10.2 Opportunistic diseases
10.2.1
Isoniazid preventive therapy (IPT)
10.2.2
Oppurtunistic infection prophylaxis, with
cotrimoxazole
10.2.3
Candidiasis of oesophagus/trachea/bronchi
10.2.4
Cryptococcosis
10.2.4.1 Asymptomatic cryptococcosis, CrAg
positive
10.2.4.2 Symptomatic, non-meningeal
cryptococcosis
10.2.4.3 Cryptococcal meningitis
10.2.5
Cryptosporidiosis diarrhoea
10.2.6
Cytomegalovirus (CMV)
10.2.7
Isosporiasis
10.2.8
Mycobacteriosis – disseminated non-tuberculous
10.2.9
Pneumocystis pneumonia
10.2.10 Cerebral toxoplasmosis
10.3 Kaposi sarcoma (KS)
10.4 Post-exposure prophylaxis
10.4.1
Post-exposure prophylaxis, occupational
10.4.2
Non occupational post exposure prophylaxis,
sexual assault and inadvertent exposure
10.1
10.1
10.6
10.7
CHAPTER 11 – SURGICAL ANTIBIOTIC PROPHYLAXIS
General Principles
Antibiotic Prophylaxis
Special Considerations
Process Measure
11.1
11.1
11.2
11.4
11.4
xii
10.14
10.15
10.15
10.16
10.16
10.17
10.17
10.19
10.19
10.20
10.21
10.22
10.22
10.23
10.24
10.25
10.26
10.26
10.29
TABLE OF CONTENTS
CHAPTER 12 - ANAESTHESIOLOGY, PAIN AND INTENSIVE CARE
12.1
12.1
12.2
12.1
12.1
12.1
12.2
12.2
12.2
12.2
12.2
12.3
12.3
12.4
12.4
12.5
12.5
12.5
12.6
12.7
12.7
12.3
12.4
12.5
12.6
12.7
12.8
12.9
12.10
12.11
12.12
Premedication
General anaesthesia
12.2.1 Intravenous induction (and/or maintenance) agents
12.2.2 Inhalation agents
12.2.2.1
Induction
12.2.2.2
Maintenance
Muscle relaxants
12.3.1
Depolarising muscle relaxants
12.3.2
Non-depolarising muscle relaxants (NDMRs)
12.3.3
Muscle relaxation for rapid sequence intubation
12.3.4
Medicines to reverse muscle relaxation
Perioperative analgesia
12.4.1
Perioperative analgesics
12.4.1.1 Oral analgesics
12.4.1.2 Intravenous analgesics
12.4.2
Postoperative pain in the recovery room
12.4.3
Postoperative analgesia ward prescriptions
12.4.3.1 Examples of ward prescriptions for
postoperative analgesia according to
anticipated pain severity
Intravenous fluids
12.5.1
Crystalloids
Medicines to treat complications of anaesthesia
12.6.1
Malignant hyperthermia
12.6.2
Local anaesthetic toxicity
12.6.3
Anaesthetic-related acute hypotension
12.6.4
Anaesthesia-related acute hypertension
12.6.5
Postoperative nausea and vomiting (PONV)
12.6.5.1 Prevention of PONV
12.6.5.2 Treatment of PONV
12.6.6
Acid aspiration prophylaxis
Spinal (intrathecal) anaesthesia
12.7.1
Anticoagulants and spinal or epidural blocks
Epidural anaesthesia
Peripheral nerve block or wound infiltration
Topical anaesthesia
Sedation
Pain, chronic
12.12.1 Analgesia for chronic non-cancer pain
12.12.2 Analgesia for chronic cancer pain
12.12.3 Treatment of adverse effects of chronic opioid use
12.12.4 Analgesia for chronic neuropathic pain
12.12.5 Analgesia for acute non-surgical pain
12.12.5.1
Medical conditions associated
with severe pain
xiii
12.8
12.8
12.9
12.9
12.9
12.9
12.10
12.10
12.10
12.11
12.12
12.12
12.12
12.13
12.14
12.14
12.15
12.15
12.16
12.17
12.17
12.18
12.18
12.18
TABLE OF CONTENTS
12.12.5.2
12.13
Acute pain due to gastrointestinal
colic
Intensive care
12.13.1 Nutritional support
12.19
12.19
12.19
CHAPTER 13 - MUSCULOSKELETAL SYSTEM
13.1
Arthritis, rheumatoid (RA)
13.2
Arthritis, septic and osteomyelitis, acute
13.3
Osteo-arthritis
13.4
Gout
13.5
Seronegative spondylarthritis
13.5.1
Arthritis, reactive
13.6
Systemic lupus erythematosus (SLE)
13.1
13.1
13.4
13.5
13.7
13.9
13.10
13.10
CHAPTER 14 - NEUROLOGICAL DISORDERS
14.1
Cerebrovascular disease
14.1.1
Stroke
14.1.2
Transient ischaemic attach (TIA)
14.1.3
Acute spinal cord injury
14.1.4
Subarachnoid haemorrhage
14.2
Dementia
14.3
Epilepsy
14.3.1
Status epilepticus
14.4
Headache and facial pain syndromes
14.4.1
Migraine
14.4.2
Cluster headache
14.4.3
Trigeminal neuralgia
14.4.4
Tension headache
14.4.5
Idiopathic intracranial hypertension
(Pseudotumour cerebri)
14.5
Infectious and parasitic conditions
14.5.1
Meningitis
14.5.2
Viral meningoencephalitis
14.5.3
Meningovascular syphilis
14.5.4
Brain abscess
14.5.5
Antimicrobial use in patients with head injuries
14.5.6
Neurocysticercosis
14.6
Movement disorders
14.6.1
Parkinsonism
14.6.2
Essential tremor
14.6.3
Chorea
14.7
Neuropathy
14.8
Acute myelopathy
14.9
Multiple sclerosis
14.10 Myasthenia gravis
14.11 Oedema, cerebral
14.11.1 Brain oedema due to tumours and inflammation
14.1
14.1
14.1
14.3
14.4
14.4
14.5
14.6
14.10
14.11
14.11
14.12
14.13
14.13
14.14
xiv
14.15
14.15
14.18
14.19
14.19
14.20
14.20
14.20
14.21
14.22
14.22
14.23
14.24
14.25
14.25
14.25
14.25
TABLE OF CONTENTS
14.11.2
Brain oedema due to traumatic injury
14.26
CHAPTER 15 - PSYCHIATRIC DISORDERS
15.1
Aggressive disruptive behaviour in adults
15.2
Confusional states/delirium
15.3
Bipolar disorder
15.4
Depressive disorder, major
15.5
Persistent depressive disorder (Dysthymic disorder)
15.6
Generalised anxiety disorder
15.7
Obsessive-compulsive disorder
15.8
Panic disorder
15.9
Acute stress disorder and post-traumatic stress disorder
15.10 Psychosis, acute
15.11 Schizophrenia
15.12 Withdrawal from substances of abuse
15.12.1
Alcohol
15.12.2
Alcohol withdrawal delirium (Delirium tremens)
15.12.3
Opiate withdrawal,e.g. heroin
15.12.4
Stimulant withdrawal, including cocaine and
methamphetamines
15.12.5
Methaqualone withdrawal
15.12.6
Cannabis withdrawal
15.12.7
Benzodiazepine withdrawal
15.13 Insomnia
15.14 Discontinuation symptoms of serotonin reuptake inhibitors
15.1
15.1
15.3
15.4
15.8
15.9
15.10
15.11
15.11
15.12
15.14
15.14
15.16
15.16
15.17
15.18
15.20
CHAPTER 16 - RESPIRATORY SYSTEM
16.1
Asthma, acute
16.2
Asthma, chronic persistent
16.3
Bronchiectasis
16.4
Chronic obstructive pulmonary disease (COPD)
16.5
Lung abscess
16.6
Pneumonia, community acquired
16.7
Pneumonia, aspiration
16.8
Empyema
16.9
Tuberculosis, pulmonary
16.10 Tuberculosis, pleural (TB pleurisy)
16.11 Drug-resistant TB
16.11.1
INH monoresistant TB
16.11.2
Multidrug-resistant TB
16.1
16.1
16.2
16.5
16.7
16.11
16.11
16.14
16.14
16.15
16.17
16.18
16.18
16.19
CHAPTER 17 - EAR, NOSE AND THROAT DISORDERS
17.1
Epiglottitis
17.2
Rhinitis, allergic, persistent
17.3
Sinusitis, bacterial, complicated
17.4
Otitis media, acute
17.5
Otitis media, chronic, suppurative
17.6
Mastoiditis
17.1
17.1
17.2
17.2
17.3
17.4
17.5
xv
15.20
15.21
15.21
15.22
15.23
TABLE OF CONTENTS
17.7
17.8
17.9
Otitis externa
17.7.1
Otitis externa, necrotising
Abscess, peritonsillar
Vertigo, acute
17.5
17.5
17.6
17.7
CHAPTER 18 - EYE DISORDERS
18.1
Conjunctivitis
18.1.1
Conjunctivitis, adenoviral
18.1.2
Conjunctivitis, allergic
18.1.3
Conjunctivitis, bacterial
18.2
Endophthalmitis, bacterial
18.3
Glaucoma
18.4
Herpes zoster ophthalmicus
18.5
Keratitis
18.5.1
Keratitis, herpes simplex
18.5.2
Keratitis, suppurative
18.6
Retinitis, HIV CMV
18.7
Uveitis
18.8
Surgical and diagnostic products
18.9
Dry eye
18.10 Medical management of eye injury
18.10.1
Chemical burn
18.10.2
Eye injury: blunt/penetrating/foreign body
18.1
18.1
18.1
18.2
18.2
18.3
18.4
18.6
18.6
18.6
18.7
18.7
18.8
18.8
18.9
18.10
18.10
18.10
CHAPTER 19 - POISONING
Poison Centres
Envenomation
19.1
Insect bites and stings
19.2
Snakebites
19.2.1
Boomslang snake bite
19.2.2
Venom in the eye
19.3
Scorpion envenomation
19.4
Spider envenomation
Exposure To Poisonous Substances
19.5
Analgesic poisoning
19.5.1
Paracetamol poisoning
19.5.2
Salicylate poisoning
19.5.3
Opioid poisoning
19.6
Antidepressants
19.6.1
Tricyclic antidepressant poisoning
19.7
Iron poisoning
19.8
Theophylline poisoning
19.9
Sedative hypnotic poisoning
19.9.1
Benzodiazepine poisoning
19.9.2
Lithium poisoning
19.10 Isoniazid poisoning
19.11 Calcium channel blocker poisoning
19.1
19.1
19.1
19.1
19.2
19.6
19.6
19.7
19.8
19.10
19.12
19.12
19.14
19.14
19.15
19.15
19.17
19.18
19.19
19.19
19.19
19.20
19.20
xvi
TABLE OF CONTENTS
19.12
19.13
19.14
19.15
19.16
19.17
19.18
19.19
19.20
19.21
19.22
Cotrimoxazole poisoning
Antiretroviral agents poisoning
Illicit drugs
19.14.1
Cocaine poisoning
19.14.2
Poisoning with amphetamine derivatives
Hydrocarbon poisoning
Ingestion of caustic substances
Alcohols
19.17.1
Ethanol poisoning
19.17.2
Ethylene glycol poisoning
19.17.3
Methanol poisoning
Pesticides and rodenticides
19.18.1
Amitraz poisoning
19.18.2
Organophosphate poisoning
19.18.3
Paraquat poisoning
Anticoagulant poisoning
Carbon monoxide poisoning
Heavy metal poisoning
Poisoning with substances that cause
methaemoglobinaemia
19.21
19.21
19.22
19.22
19.23
19.24
19.25
19.25
19.25
19.26
19.27
19.27
19.27
19.28
19.29
19.29
19.31
19.32
19.32
CHAPTER 20 - EMERGENCIES AND INJURIES
20.1
Emergencies
20.1.1
Angioedema
20.1.2
Anaphylaxis/anaphylactic shock
20.1.3
Hypovolaemic shock
20.1.4
Distributive shock
20.1.4.1
Neurogenic shock
20.1.4.2
Septic shock
20.1.5
Cardiogenic shock
20.1.6
Obstructive shock
20.1.7
Pulmonary oedema, acute
20.2
Injuries
20.2.1
Burns
20.3
Cardiac arrest – cardiopulmonary resuscitation
20.3.1
Cardiac arrest adults
20.1
20.1
20.1
20.2
20.3
20.3
20.3
20.5
20.5
20.6
20.6
20.8
20.8
20.11
20.12
CHAPTER 21 - ONCOLOGY
21.1
Malignancies
21.1
21.1
CHAPTER 22 - MEDICINES USED FOR DIAGNOSIS
22.1
Diagnostic contrast agents and related substances
22.1
22.1
CHAPTER 23 - SEDATION
23.1
Sedation
23.1.1
Procedural sedation and analgesia
23.1.2
Sedation in intensive care
23.1.3
Sedation in palliative care
23.1
23.1
23.1
23.4
23.5
xvii
TABLE OF CONTENTS
Appendix I: Antimicrobial medicines
AI.1
Appendix II: Prescribing information for specific medicines
AII.1
Guideline for the motivation of a new medicine on the National
Essential Medicines List
xxxvi
Guidelines for adverse drug reaction reporting
xli
Disease notification procedures
xlix
Index of disease conditions
lii
Index of medicines
lxi
Abbreviations
lxxi
Peak expiratory flow rates
lxxvi
Asthma Control Test®
lxxviii
Useful contact numbers and url links
lxxix
xviii
THE ESSENTIAL MEDICINES CONCEPT
The WHO describes Essential medicines as those that satisfy the priority
health care needs of the population. Essential medicines are intended to be
available within the context of functioning health systems at all times in
adequate quantities, in the appropriate dosage forms, with assured quality
and adequate information, and at a price the individual and the community
can afford.
The concept of essential medicines is forward-looking. It incorporates the
need to regularly update medicines selections to:
» reflect new therapeutic options and changing therapeutic needs;
» the need to ensure medicine quality; and
»
the need for continued development of better medicines, medicines for
emerging diseases, and medicines to meet changing resistance
patterns.
Effective health care requires a judicious balance between preventive and
curative services. A crucial and often deficient element in curative services is
an adequate supply of appropriate medicines. In the health objectives of the
National Drug Policy, the government of South Africa clearly outlines its
commitment to ensuring availability and accessibility of medicines for all
people. These are as follows:
» To ensure the availability and accessibility of essential medicines to all
citizens.
» To ensure the safety, efficacy and quality of medicines.
» To ensure good prescribing and dispensing practices.
» To promote the rational use of drugs by prescribers, dispensers and
patients through provision of the necessary training, education and
information.
» To promote the concept of individual responsibility for health, preventive
care and informed decision-making.
Achieving these objectives requires a comprehensive strategy that not only
includes improved supply and distribution, but also appropriate and extensive
human resource development. The implementation of an Essential Drugs
Programme (EDP) forms an integral part of this strategy, with continued
rationalisation of the variety of medicines available in the public sector as a
first priority. The private sector is encouraged to use these guidelines and
medicine list wherever appropriate.
xix
The criteria for the selection of essential medicines for Adult Hospital level
care in South Africa were based on the WHO guidelines for drawing up a
national EDL. Essential medicines are selected with due regard to disease
prevalence, evidence on efficacy and safety, and comparative cost.
The implementation of the concept of essential medicines is intended to be
flexible and adaptable to many different situations. It remains a national
responsibility to determine which medicines are regarded as essential.
xx
HOW TO USE THIS BOOK
Principles
The National Drug Policy makes provision for an Essential Drugs Program
which is a key component in promoting rational medicines use.
The perspective adopted in the Adult Hospital Level Standard Treatment
Guidelines (STGs) is that of a competent medical officer practicing in a public
sector hospital. The STGs serve as a standard for practice, but do not replace
sound clinical judgment. It is important to remember that the recommended
treatments provided in this book are guidelines only and are based on the
assumption that prescribers are competent to handle patients with the relevant
conditions presenting to their facilities.
All reasonable steps have been taken to align the STGs with Department of
Health guidelines that were available at the time of review. Each treatment
guideline in the Adult Hospital Level STGs and Essential Medicines List (EML)
has been designed as a progression in care from the current Primary Health
Care (PHC) STGs and EML. A medicine is included or removed from the EML
using an evidence based review of safety and effectiveness, followed by
considerations of cost and other relevant practice factors. Where a referral to a
tertiary facility is recommended, the relevant medicines have either been
reviewed or included in the tertiary level EML, or is in the process of being
reviewed. Given that the PHC STGs and EML are reviewed prior to the Adult
Hospital Level STGs, there may be a period when the two STGs are not always
perfectly aligned.
The dosing regimens provide the recommended doses used in usual
circumstances. However, the prescribed dose should take into consideration
drug-drug interactions and co-morbid states, notably renal or hepatic failure,
critical illness, and morbid obesity.
It is anticipated that each Province will review the EML and prevailing tenders
to compile a formulary which:
» Lists formulations and pack sizes that will facilitate care in alignment with
the STGs.
» Selects the preferred member of the therapeutic class based on cost.
» Implements formulary restrictions consistent with the local environment.
» Provides information regarding the prices of medicines.
Therapeutic classes are designated in the “Medicine treatment” section of the
STGs followed by an example such as, HMGCoA reductase inhibitors (statins)
e.g. simvastatin. These therapeutic classes have been designated where none of
the members of the class offer a significant benefit over the other registered
members of the class. Always consult the local formulary to identify the example
from the therapeutic class that has been approved for use in your facility.
Navigating the book
It is important that you become familiar with the contents and layout of the book
xxi
in order to use the STGs effectively.
The International Classification of Diseases (ICD)-10 number has been
included with the conditions to facilitate accurate recording of diagnoses. A
brief description and diagnostic criteria are included to assist the medical
officer to make a diagnosis. These guidelines also provide guidelines for
referral of patients with more complex and uncommon conditions to tertiary
facilities with the resources for further investigation and management.
The STGs are arranged into chapters according to the organ systems of the
body. Conditions and medicines are cross referenced in two separate indexes
of the book. In some therapeutic areas that are not easily amenable to the
development of a STG, the section is limited to a list of medicines.
This edition of the Adult Hospital Level STG and EML provides additional
information: a quick reference to dosing of antimicrobials for specific
indications (Appendix I) and a section providing guidance on special
considerations for specific medicines (Appendix II).
Furthermore, to promote transparency, in this fifth edition, revisions are
accompanied by the level of evidence that is cited and hyperlinked accordingly.
All evidence is graded according to the Strength Of Recommendation
Taxonomy (SORT) (a patient-centered approach to grading evidence in the
medical literature), described in detail on page xxxviii.
The section on Patient Education in Chronic Conditions aims to assist health
workers to improve patient adherence and health, generally.
Glossary
Term:
16+6 gestation weeks
Child Pugh score (A,B,C)
Morbid obesity
Renal failure
Severe penicillin allergy
Surgical prophylaxis
Description:
Second trimester:16 weeks and 6 days pregnant
Prognostic scoring tool for chronic liver disease
Obesity sufficient to prevent normal activity or
physiologic function, or to cause the onset of a
pathologic condition; BMI ≥ 40 kg/m2.
eGFR < 30 mL/minute.
A history of anaphylaxis, urticaria or angioedema
associated with beta-lactam antimicrobials.
Prophylactic antibiotic therapy that reduces the risk of
surgical site infection. In most instances a single
antibiotic dose prior to the procedure is sufficient.
Postoperative antimicrobial administration is not
recommended for most surgeries as this selects for
antimicrobial resistance.
Medicines Safety
Provincial and local Pharmaceutical and Therapeutics Committees (PTCs) should
develop medicines safety systems to obtain information regarding medication
errors, prevalence and importance of adverse medicine events, interactions and
medicines quality. These systems should not only support the regulatory
pharmacovigilance plan, but should also provide pharmacoepidemiology data
xxii
that will be required to inform future essential medicines decisions as well as local
interventions to improve safety.
In accordance with the Medicines Control Council’s guidance on reporting
adverse drug reactions in South Africa, the medical officer with the support of
the PTC should report the relevant adverse reactions to the National Adverse
Drug Event Monitoring Centre (NADEMC). To facilitate reporting a copy of the
form and guidance on its use has been provided at the back of the book.
Feedback
Comments that aim to improve these treatment guidelines will be appreciated.
The submission form and guidelines for completing the form are included in the
book. Motivations will only be accepted from the Provincial PTC.
THERAPEUTIC DRUG MONITORING (TDM)
Potentially toxic medicines, medicines with narrow therapeutic indices and
those with variable pharmacokinetics should be monitored regularly to optimise
dosing, obtain maximum therapeutic effect, limit toxicity and assess
compliance. Appendix II provides detailed information for specific medicines.
Lithium
Measure serum levels at about 12 hours after the last dose – e.g. in the
morning before that day’s first dose. Levels should be less than 1 mmol/L and
should be checked regularly while on therapy, with more frequent monitoring in
the elderly and frail.
Aminoglycosides
Peak levels will generally be adequate if dosing is adequate (e.g. gentamicin 5
mg/kg/day in a single daily dose) and are not recommended unless the
organism has a high MIC or the patient is critically ill. Trough levels taken
immediately before the next dose are valuable in identifying potential toxicity
before it manifests as deafness or renal impairment. Aminoglycosides are
relatively contraindicated in renal impairment.
Anti-epileptics
Levels may be helpful to confirm poor adherence or to confirm a clinical
suspicion of toxicity. Routine measurement in patients with well controlled
seizures and no clinical evidence of toxicity, is not appropriate. Individual levels
may be difficult to interpret – if in doubt, seek assistance from a clinical
pharmacologist/pharmacokineticist.
PRESCRIPTION WRITING
Medicines should be prescribed only when they are necessary for treatments
following clear diagnosis. Not all patients or conditions need prescriptions for
medicine. In certain conditions simple advice and general and supportive
measures may be more suitable.
In all cases carefully consider the expected benefit of a prescribed medication
xxiii
against potential risks. This is important during pregnancy where the risk to
both mother and foetus must be considered.
All prescriptions should:
» be written legibly in ink by the prescriber with the full name and address of
the patient, and signed with the date on the prescription form;
» specify the age and, in the case of children, weight of the patient;
» have contact details of the prescriber e.g. name and telephone number.
In all prescription writing the following should be noted:
» The name of the medicine or preparation should be written in full using the
generic name.
» No abbreviations should be used due to the risk of misinterpretation. Avoid
the Greek mu (ų): write mcg as an abbreviation for micrograms.
» Avoid unnecessary use of decimal points and only use where decimal points
are unavoidable. A zero should be written in front of the decimal point where
there is no other figure, e.g. 2 mg not 2.0 mg or 0.5 mL and not .5 mL.
» Frequency: Avoid Greek and Roman frequency abbreviations that cause
considerable confusion (qid, qod, tds, tid, etc). Instead either state the
frequency in terms of hours (e.g. 8 hourly) or times per day in numerals (e.g.
3x/d).
» State the treatment regimen in full:
 medicine name and strength,
 dose or dosage,
 dose frequency,
 duration of treatment,
e.g. amoxicillin 500 mg 8 hourly for 5 days.
» In the case of “as required”, a minimum dose interval should be specified,
e.g. every 4 hours as required.
» Most monthly outpatient scripts for chronic medication are for 28 days;
check that the patient will be able to access a repeat before the 28 days
are completed.
» After writing a script, check that the dose, dose units, route, frequency,
and duration for each item is stated. Consider whether the number of
items is too great to be practical for the patient, and check that there are
no redundant items or potentially important drug interactions. Check that
the script is dated and that the patient’s name and folder number are on
the prescription form. Only then sign the script, and as well as signing
provide some other way for the pharmacy staff to identify you if there are
problems (print your name, use a stamp, or use a prescriber number from
your institution’s pharmacy).
xxiv
Notes on specific medicines
ACE-inhibitor
ACE-inhibitors and
ARBs
Allopurinol
Amitriptyline +
citalopram
Anti-epileptic
medicines
Benzodiazepines
ß–blockers
Ceftriaxone
Ciprofloxacin
Clindamycin
Folic acid + vitamin
B12
Haloperidol
Angioedema is a potentially serious complication of ACEinhibitor treatment and if it occurs it is a contraindication to
continued therapy or to re-challenge
ACE-inhibitors and ARBs can cause or exacerbate
hyperkalaemia in CKD (eGFR < 60 mL/minute). Check the
serum potassium before starting these medicines, and monitor
serum
potassium
on
therapy.
ACE-inhibitors and ARBs are contra-indicated in pregnancy.
Contra-indicated in patients with eGFR < 30 mL/minute.
Do not stop uric acid lowering drugs during an acute attack.
Concomitant use of amitriptyline and citalopram may increase
the risk of serotonin syndrome or neuroleptic malignant
syndrome. Furthermore, there is a potential risk for QT
prolongation.
Phenytoin, phenobarbitone and carbamazepine are potent
enzyme inducing agents and should be used with caution with
other medicines metabolised by the liver, especially warfarin,
ARVs, progestin subdermal implants and oral contraceptives.
Benzodiazepines can cause respiratory depression.
Monitor patients closely as benzodiazepines can exacerbate
an abnormal mental state or mask important neurological signs
of
deterioration.
Prolonged treatment with benzodiazepines often leads to
tolerance and withdrawal symptoms if the medicine is
discontinued
abruptly.
Combination therapy with more than one benzodiazepine is
not indicated.
ß–blockers should not be used in cocaine poisoning.
ß–blockers may cause bronchospasm in asthmatics.
Severe bacterial infections can mimic the features of
haemorrhagic fever syndrome, and broad spectrum antibiotics,
e.g. ceftriaxone, IV, 2 g daily, are indicated in every case until
the diagnosis is confirmed.
Irrational use of quinolones contributes to the emergence of
XDR-TB and potential masking of active TB.
Clindamycin has good coverage against Gram positive
organisms and anaerobes, so the addition of metronidazole
is unnecessary.
Anemia megaloblastic: Give vitamin B12 and folic acid
together until the test results are available as giving folic acid
alone in patients with a B12 deficiency may precipitate
a permanent neurological deficit.
Dosing may vary according to clinical circumstances, e.g.
lower doses in the elderly or where HIV infection or HIVrelated dementia is known or suspected. In the frail and
elderly patient, reduce the dose by half.
xxv
Lithium
Loperamide
Low molecular weight
heparin (LMWH)
Lyophilised plasma
Metformin
Metronidazole
Misoprostol (for TOP)
Moxifloxacin
NSAIDs
Oral diabetic agents
Potassium
Antivenom
Therapeutic drug monitoring is essential when using lithium.
Clinical toxicity may occur even within the therapeutic range.
Concomitant use of many medicines e.g. ACE-inhibitors,
NSAIDs and diuretics may increase the risk of lithium toxicity.
Contraindicated in dysentery, acute non-inflammatory
diarrhoea, antibiotic-associated diarrhoea and amoebic
dyssentery; as it may result in toxic megacolon
In morbid obesity dosing of LMWH should be individualised,
in discussion with a specialist.
In renal failure (eGFR < 30 mL/minute), the recommended
dose of LMWH is 1 mg/kg/day. Pregnant women with
mechanical prosthetic valves should not receive LMWH
unless antifactor Xa levels can be monitored reliably weekly.
Therapeutic range is pre-dosing level 0.6 units/mL and a 4hour peak level of 1–1.2 units/mL.
An alternative to fresh frozen plasma, based on limited
evidence of efficacy. Does not require crossmatch prior to
infusion, can be stored at room temperature and is pathogen
inactivated (via a solvent detergent inactivation procedure).
Metformin should be dose adjusted in renal impairment
(eGFR: 30-60 mL/minute).
The addition of metronidazole to amoxicillin/clavulanic acid is
unnecessary as amoxicillin/clavulanic acid has adequate
anaerobic cover.
Misoprostol can cause uterine rupture in women with previous
Caesarean sections and those of high parity. In these women
use 200 mcg of misoprostol or alternative methods such as
extra-amniotic saline infusion without misoprostol. The dose of
misoprostol, PV, decreases with increasing gestational age
because of the risk of uterine rupture.
Restricted for use in MDR-TB and in cases of severe penicillin
allergy for specific indications (i.e. Hospital-acquired pneumonia,
bronchiectasis, lung abscess, community acquired pneumonia,
aspiration pneumonia and empyema).
Concomitant use of more than one NSAID has no additional
clinical benefit and only increases toxicity. Chronic use of all
NSAIDs is associated with varying degrees of gastrointestinal,
renal and cardiovascular risks. Long-term use of NSAIDs
should weigh potential benefits against these risks.
Oral diabetic agents should not be used in type 1 diabetes and
used with caution in liver and renal impairment.
Potassium will fall on insulin treatment and patients with DKA
have potassium depletion even if initial potassium is normal or
high. It is therefore essential to monitor and replace potassium.
Never administer antivenom without being fully prepared to
manage acute anaphylaxis.
xxvi
Prednisone taper
Silver sulfadiazine
Sodium chloride
Spironolactone
SSRIs
Streptokinase
Sulphonylureas
Tricyclic
antidepressants
Testosterone
Topical retinoids
Unfractionated heparin
Valproate
Verapamil
Warfarin
Example of a dose reduction regimen, for an initial dose of
60 mg daily, reduce initial dose by 2/3, and continue as
follows:
» 40 mg/day in week 2,
» 25 mg/day in week 3,
» 20 mg/day in week 4,
» 15 mg/day in week 5,
» 10 mg /day in week 6 and
» thereafter 5 mg daily for 1 week and then discontinue.
Note: Weaning should be adjusted according to clinical
context. If control deteriorates on weaning return to the
previous effective dose.
Do not use silver sulfadiazine if SJS/TEN is thought to be due
to cotrimoxazole or other sulphonamide.
Rapid correction of sodium, in hyponatraemia, may lead to
central pontine myelinolysis, which is often irreversible. Sodium
should be frequently monitored and increases should be <9
mmol/L per day.
Monitoring of sodium, potassium and renal function is essential
in patients taking spironolactone. Avoid if eGFR < 30
mL/minute.
Adolescents with depression may have an increased risk of
suicidal ideation when initiated on SSRIs.
Do not use heparin if streptokinase is given.
Hypoglycaemia caused by a sulphonylurea can be prolonged.
The patient should be hospitalised with an intravenous glucose
infusion, and observed for at least 12 hours after glucose
infusion has stopped.
Avoid in patients with cardiac disease and a high risk of
overdose.
Screen hypogonadal men for prostate cancer before beginning
testosterone replacement.
Do not use in pregnant women.
Evidence indicates that PTT monitoring is not necessary with
weight based dosing of unfractionated heparin. However, in
patients with morbid obesity and renal failure (eGFR < 30
mL/minute) unfractionated heparin should be used with PTT
monitoring to maintain the PTT at 1.5 to 2.5 times the control.
PTT should be taken 4 hours after SC dose.
Do not initiate valproate during pregnancy, or if a woman
intends to fall pregnant, as it is associated with a higher
teratogenic potential than the other first line anti-epileptic
agents.
Never give verapamil or adenosine IV to patients with a wide
QRS tachycardia as this may precipitate ventricular fibrillation.
In atrial flutter, do not use verapamil as it will not convert flutter
to sinus rhythm and may cause serious hypotension.
Warfarin use requires regular INR monitoring and dose
adjustment according to measured INR. See appendix II
xxvii
PENICILLIN DESENSITISATION
This has been included for information only.
Perform only in an ICU setting.
Discontinue all ß-adrenergic antagonists. Have an IV line, ECG monitor and
spirometer in place. Once desensitised, treatment must not lapse as risk of
subsequent allergy increases.
A history of Stevens-Johnson’s syndrome, exfoliative dermatitis, erythroderma
are absolute contra-indications to desensitisation (use only as an approach to
IgE sensitivity).
Oral route is preferred. 1/3 of patients develop a transient reaction during
desensitisation or treatment, which is usually mild.
A: Reconstitute phenoxymethylpenicillin 250 mg/ 5mL
Step
Medicine mg/mL
Amount to administer (mL)
Strictly every 15 minutes
B: To make 0.5 mg/mL solution:
Dilute 0.5 mL of reconstituted phenoxymethylpenicillin
solution in 49.5 mL water.
1
0.1 mL
2
0.2 mL
0.5 mg/mL solution
3
0.4 mL
(1000 units/mL)
4
0.8 mL
5
1.6 mL
6
3.2 mL
7
6.4 mL
C: To make 05 mg/mL solution:
Dilute 1 mL of reconstituted phenoxymethylpenicillin solution
in 9 mL water.
8
1.2 mL
5 mg/mL solution
9
2.4 mL
(10000 units/mL)
10
4.8 mL
D: Reconstituted phenoxymethylpenicillin
250mg/ 5mL = 50 mg/mL
11
1.0 mL
50 mg/mL
12
2.0 mL
(80000 units/mL)
13
4.0 mL
14
8.0 mL
After step 14, observe for 30 minutes, then give 1.0 g IV.
Interval between doses: 15 minutes.
xxviii
Parenteral route
Step
Medicine mg/mL
Amount to administer (mL)
Strictly every 15 minutes:
1
0.1 mL
0.1 mg/mL
2
0.2 mL
3
0.4 mL
4
0.8 mL
5
0.16 mL
1 mg/mL
6
0.32 mL
7
0.64 mL
8
0.12 mL
10 mg/mL
9
0.24 mL
10
0.48 mL
11
0.1 mL
12
0.2 mL
13
0.4 mL
100 mg/mL
14
0.8 mL
15
0.16 mL
16
0.32 mL
17
0.64 mL
After step 17, observe for 30 minutes, then give 1.0 g IV.
Interval between doses: 15 minutes.
COTRIMOXAZOLE DESENSITISATION
Attempt desensitisation in patients with a history of cotrimoxazole intolerance,
unless this was life-threatening, e.g.: Stevens-Johnson syndrome. (See section
4.6: Erythema Multiforme, Stevens Johnson Syndrome, Toxic Epidermal
Necrolysis). Unless the rash is severe or associated with systemic symptoms,
continue treatment with careful observation for deterioration.
Desensitisation should be attempted using cotrimoxazole suspension 240
mg/5ml. Dilute the suspension appropriately and consult with your pharmacist if
necessary.
Note: Do not administer antihistamines or steroids with this regimen.
Time (hours)
0
1
2
3
4
5
Cotrimoxazole dose (mL of 240mg/5mL
suspension
0.0005
0.005
0.05
0.5
5
Two single strength tablets (each tablet =
80/400 mg) followed by full dose
xxix
A GUIDE TO PATIENT ADHERENCE IN CHRONIC
CONDITIONS
Achieving health goals for chronic conditions such as asthma, diabetes, HIV
and AIDS, epilepsy, hypertension, mental health disorders and TB requires
attention to:
» Adherence to long term pharmacotherapy – incomplete or non-adherence
can lead to failure of an otherwise sound pharmacotherapeutic regimen.
» Organisation of health care services, which includes consideration of
access to medicines and continuity of care.
Patient Adherence
Adherence is the extent to which a person’s behaviour – taking medication,
following a diet and/or executing lifestyle changes, corresponds with agreed
recommendations from a health care provider.
Poor adherence results in less than optimal management and control of the
illness and is often the primary reason for suboptimal clinical benefit. It can
result in medical and psychosocial complications of disease, reduced quality of
life of patients, and wasted health care resources.
Poor adherence can fall into one of the following patterns where the patient:
» takes the medication very rarely (once a week or once a month);
» alternates between long periods of taking and not taking their medication, e.g.
after a seizure or BP reading;
» skips entire days of medication;
» skips doses of the medication;
» skips one type of medication;
» takes the medication several hours late;
» does not stick to the eating or drinking requirements of the medication;
» adheres to a purposely modified regimen; and
» adheres to an unknowingly incorrect regimen.
Adherence should be assessed on a regular basis. Although there is no gold
standard, the current consensus is that a multi method approach that includes
self report be adopted, as indicated below.
Barriers that contribute toward poor adherence:
BARRIER
RECOMMENDED SUPPORT
Life style
» It is often difficult to take multiple
medications.
» A busy schedule makes it difficult to
remember to take the medication.
» Create a treatment plan with information on
how and when to take the medications.
» Use reminders such as cues that form part of
the daily routine.
xxx
BARRIER
RECOMMENDED SUPPORT
Attitudes and beliefs
» The condition is misunderstood or denied.
» Treatment may not seem to be necessary.
» May have
treatment.
low
expectations
about
» Remind patients that they have a long term
illness that requires their involvement.
» Use change techniques such as motivational
interviewing.
» Identify goals to demonstrate improvement/
stabilisation.
Social and economic
» May lack support at home or in the
community
» May not have the economic resources to
attend appointments.
» Encourage participation in treatment support
programs.
» Consider down referral or reschedule
appointment to fit in with other commitments.
Healthcare team related
» Little or no time during the visit to
provide information.
» Information maybe provided in a way
that is not understood.
» Relationship with the patient may not
promote understanding and self
management.
» Encourage patient to ask questions.
» Use patient literacy materials in the patient’s
language of choice.
» Engage active listening.
Treatment related
» Complex medication regimens (multiple
medications and doses) can be hard to
follow.
» May be discouraged if they don’t feel
better right away.
» May be concerned about adverse effects.
» If possible reduce treatment complexity.
» Help the patient understand the condition
and the role of their medication.
» Discuss treatment goals in relation to potential
adverse effects.
Although many of these recommendations require longer consultation time, this
investment is rewarded many times over during the subsequent years of
management.
For a patient to consistently adhere to long term pharmacotherapy requires
integration of the regimen into his/her daily life style. The successful integration
of the regimen is informed by the extent to which the regimen differs from his or
her established daily routine. Where the pharmacological proprieties of the
medication permits it, the pharmacotherapy dosing regimen should be adapted
to the patient’s daily routine. For example, a shift worker may need to take a
sedating medicine in the morning when working night shifts, and at night, when
working day shifts. If the intrusion into life style is too great alternative agents
should be considered if they are available. This would include situations such
as a lunchtime dose in a school-going child who remains at school for
extramural activity and is unlikely to adhere to a three times a regimen, but may
xxxi
very well succeed with a twice daily regimen.
Towards concordance when prescribing
Establish the patient’s:
» occupation,
» daily routine,
» recreational activities,
» past experiences with other medicines, and
» expectations of therapeutic outcome.
Balance these against the therapeutic alternatives identified based on clinical
findings. Any clashes between the established routine and life style with the
chosen therapy should be discussed with the patient in such a manner that the
patient will be motivated to a change in their lifestyle.
Note: Education that focuses on these identified problems is more likely to be
successful than a generic approach toward the condition/medicine.
Education points to consider
» Focus on the positive aspects of therapy whilst being encouraging
regarding the impact of the negative aspects and offer support to deal with
them if they occur.
» Provide realistic expectations regarding:
 normal progression of the illness - especially important in those
diseases where therapy merely controls the progression and those
that are asymptomatic;
 the improvement that therapy and non-medicine treatment can add to
the quality of life.
» Establish therapeutic goals and discuss them openly with the patient.
» Any action to be taken with loss of control or when side effects develop.
» In conditions that are asymptomatic or where symptoms have been
controlled, reassure the patient that this reflects therapeutic success, and
not that the condition has resolved.
» Where a patient raises concern regarding anticipated side effects, attempt
to place this in the correct context with respect to incidence, the risks vs.
the benefits, and whether or not the side effects will disappear after
continued use.
Note: Some patient’s lifestyles make certain adverse responses acceptable
which others may find intolerable. Sedation is unlikely to be acceptable to a
student but an older patient with insomnia may welcome this side effect. This is
where concordance plays a vital role.
Notes on prescribing in chronic conditions.
» Don't change doses without good reason.
» Never blame anyone or anything for non-adherence before fully
investigating the cause.
» If the clinical outcome is unsatisfactory - investigate adherence (remember
xxxii
»
»
»
»
side effects may be a problem here).
Always think about side effects and screen for them from time to time.
When prescribing a new medicine for an additional health related problem
ask yourself whether or not this medicine is being used to manage a side
effect.
Adherence with a once daily dose is best. Twice daily regimens show
agreeable adherence. However once the interval is decreased to 3 times
a day there is a sharp drop in adherence with poor adherence to 4 times a
day regimens.
Keep the total number of tablets to an absolute minimum as too many may
lead to medication dosing errors and may influence adherence
Improving Continuity of Therapy
» Make clear and concise records.
» Involvement the patient in the care plan.
» Every patient on chronic therapy should know:
 his/her diagnosis
 the name of every medicine
 the dose and interval of the regimen
 his/her BP or other readings
Note: The prescriber should reinforce this only once management of
the condition has been established.
» When the patient seeks medical attention for any other complaints such
as a cold or headache he/she must inform that person about any other
condition/disease and its management
» If a patient indicates that he/she is unable to comply with a prescribed
regimen, consider an alternative - not to treat might be one option, but be
aware of the consequences e.g. ethical implications.
xxxiii
Folder No.
Self-Reporting
Question
3
4
5
6
7
8
Date
(dd/mm/yyyy)
Patient Adherence Record
Do you sometimes find it difficult to remember to take your medicine?
When you feel better, do you sometimes stop taking your medication?
Thinking back over the past four days, have you missed any of your doses?
2
Evening
(hour)
9
/
10
Time the medication is taken
Considered
Acceptable
(Y/N)
Morning
(hour)
Sometimes if you feel worse when you take the medicine, do you stop taking it?
1
Visual Analogue Scale (VAS)
0
Medication
Pill Identification Test (PIT)
Knows the name
(Y/N)
Knows the number
of pills per dose
(Y/N)
xxxiv
/
Yes
No
Score ____%
Knows any
additional
instruction
Did the client return the medication containers?
Dispensed
–
Returned
Pill Count
–
Yes*
No
Answered ‘Yes’ to 2 or more
questions
%
Answered ‘Yes’ to 1
question
Less than 75%
X 100 =
Answered ‘No’ to all
questions
75–94%
Dose only or confused
Expected to be taken
> 95%
Dose and Time
Less than 75%
Low
75–94%
Moderate
> 95%
High
Dose, Time, and
Instructions
X 100 =
*If yes, check that the client only used medication from this container since the date of their last visit. If leftover
medication had been used or an emergency prescription obtained, then the calculation will be invalid – skip to adherence
assessment.
% Adherence =
Adherence Assessment
Self-reporting
VAS
PIT—Client knows the…
Pill count
Overall Adherence
xxxv
CHAPTER 1
ALIMENTARY TRACT
1.1 GASTROINTESTINAL DISORDERS
1.1.1 BOWEL PREPARATIONS
Bowel preparation is essential for colonoscopy.
Split-dose (half the dose the night before and half the dose on the day of
colonoscopy) bowel cleanser and no dietary restriction seems to provide
better quality colon cleansing than single doses with a liquid diet on the day
preceding colonoscopy.
GENERAL MEASURES
Health care professionals should provide both oral and written patient
education instructions and emphasize the importance of adherence to the
bowel preparation.
MEDICINE TREATMENT
Preparations containing ingredients such as polyethylene glycol (PEG), and
i
sodium sulphate are adequate for bowel cleansing.
LoE:II

PEG/sodium sulphate, oral, solution.
o 2 litres the night before the procedure and 2 litres the following
ii
morning within two hours of the procedure.
LoE:I
Routine use of adjunctive agents (e.g. bisacodyl, senna, prokinetics) for
iii
bowel cleansing before colonoscopy is not recommended.
LoE:III
1.1.2 DIVERTICULOSIS
K57.9
DESCRIPTION
Colonic diverticulosis becomes increasingly common with age. Diverticulosis
can be complicated by haemorrhage or diverticulitis. Acute diverticulitis is
inflammation of diverticulae usually accompanied by polymicrobial infection.
Acute diverticulitis is defined as complicated when there is bowel
obstruction, abscess, fistula, or perforation.
GENERAL MEASURES
Increase dietary fibre intake.
MEDICINE TREATMENT
Total duration of antibitoic therapy is 10 days, depending on clinical
response.
2015
LoE:III
1.1
CHAPTER 1
ALIMENTARY TRACT
Uncomplicated diverticulitis:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
If unable to tolerate oral therapy:

Amoxicillin/clavulanic acid, IV, 1000/200 mg 8 hourly.
iv
LoE:III
REFERRAL
»
Acute diverticulitis with clinical deterioration or failure to improve on
medical therapy.
Peritonitis.
Complicated diverticulitis (to a centre which can perform colonic
surgery).
Massive haemorrhage.
»
»
»
1.1.3 GASTRO-OESOPHAGEAL
(GORD)
REFLUX
DISEASE
K21
DESCRIPTION
A disorder which develops as a consequence of the reflux of gastric and
duodenal contents into the oesophagus. It is usually characterised by
heartburn and regurgitation. Complications that may develop in severe
disease are strictures, ulceration, Barrett’s oesophagus and adenocarcinoma
of the oesophagus. Two thirds of patients have a normal endoscopy which is
termed non-erosive reflux disease (NERD).
GENERAL MEASURES
Weight reduction is recommended if overweight.
All patients with alarm symptoms, i.e. weight loss, haematemesis or
melaena, dysphagia, or anaemia, or older than 45 years of age should have
an endoscopy.
MEDICINE TREATMENT
Proton pump inhibitors (PPIs)
A trial with a PPI confirms acid-related disease. Only if no alarm symptoms:
v
LoE:I

Lansoprazole, oral, 30 mg daily for 4 weeks.
Recurrence of symptoms
After endoscopic confirmation of disease:

Lansoprazole, oral, 30 mg daily.
o Decrease to omeprazole, oral, 10 mg daily after 4 weeks.
Barretts’ oesophagitis
Restart PPI:

Lansoprazole, oral, 30 mg daily.
Note:
»
These patients usually need maintenance PPI therapy.
2015
1.2
CHAPTER 1
ALIMENTARY TRACT
There is no convincing evidence that long-term treatment of Barrett’s
oesophagitis with PPIs reduces dysplasia or progression to
malignancy.
»
REFERRAL
Discuss with a specialist for consideration of surgery in:
»
young patients who are PPI dependent and will require life-long
therapy;
»
patients unable to take PPIs;
»
patients requiring high doses of PPIs;
»
patients with large hiatus hernias and “volume reflux”;
»
a rolling hiatus hernia with obstructive symptoms requires surgery.
1.1.4 HIATUS HERNIA
K44
See section 1.1.3: Gastro-Oesophageal Reflux Disease (GORD).
1.1.5 INFLAMMATORY BOWEL DISEASE
K50.9/K51.9/K52.9
DESCRIPTION
Inflammatory bowel disease is a chronic inflammatory disorder of the
gastrointestinal tract that includes both Crohns disease (CD) and ulcerative
colitis. Abdominal pain, rectal bleeding, diarrhoea, and weight loss
characterize both CD and ulcerative colitis.
REFERRAL
All patients with a potential diagniosis of Crohns disease or ulcerative colitis,
should be discussed with a specialist.
1.1.6 PANCREATITIS, ACUTE
K85
DESCRIPTION
Acute inflammatory condition of the pancreas.
Intense local inflammation results in pain and local as well as systemic
complications. DIC, metaboilic derangements and shock may occur.
Lipase assessment is useful to confirm the diagnosis
Renal function, electrolytes and calcium, can be used to determine severity.
Imaging is rarely needed.
GENERAL MEASURES
Nasogastric suction when persistent vomiting or ileus occurs.
Parenteral fluid replacement to correct metabolic and
disturbances.
2015
electrolyte
1.3
CHAPTER 1
ALIMENTARY TRACT
Parenteral nutrition is associated with adverse outcomes and should only be
considered in patients that cannot receive or tolerate nasogastric or enteral
nutrition.
Drainage of abscess, psuedocyst, if required.
MEDICINE TREATMENT
For pain:

Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Acute symptomatic hypocalcaemia

Calcium gluconate 10%, IV infusion, 10 mL as a bolus over 10 minutes.
o Follow with 60–120 mL diluted in 1 L sodium chloride 0.9%,
administered over 12–24 hours.
o Monitor serum calcium at least 12 hourly.
LoE:III
If serum magnesium < 0.5 mmol/L:
ADD

Magnesium sulphate, IV infusion, 25–50 mmol in 12–24 hours.
o 1 mL magnesium sulphate 50% = 2 mmol magnesium.
Antimicrobial therapy
The administration of prophylactic antibiotics is not necessary.
For abscess of the pancreas:
Broad spectrum IV antibiotics:

Amoxicillin/clavulanic acid, IV, 1000/200 mg 8 hourly for 10 days,
vi
depending on clinical response.
LoE:III
1.1.7 PANCREATITIS, CHRONIC
K86.1
DESCRIPTION
Chronic inflammatory condition of the pancreas, which results in functional
and structural damage. In most patients this is a chronic progressive disease
leading to exocrine and/or endocrine insufficiency.
GENERAL MEASURES
Abstinence from alcohol reduces abdominal pain in the early stages of the
disease.
Small frequent meals, and restricted fat intake reduces pancreatic
secretion and pain.
Elemental diets (i.e. parenteral or enteral nutrition) in chronically debilitated
patients.
When weight loss is not responding to exogenous enzymes and diet,
consider supplementation with medium chain triglycerides.
There is a risk of developing cancer of the pancreas. This should be
2015
1.4
CHAPTER 1
ALIMENTARY TRACT
considered in patients who develop worsening pain, new onset diabetes or
deterioration in exocrine function.
Dietary advice by dietician.
MEDICINE TREATMENT
Treatment is aimed at:
» pain,
» malabsorption, and
» endocrine function. See section 8.5.2: Type 1 Diabetes mellitus.
Analgesia
See Section 12.12: Pain, chronic.
Note: Pancreatic enzymes may reduce pain by negative feedback on
pancreatic secretion.
Malabsorption
Start treatment when >7 g (or 21 mmol) fat in faeces/24 hours while on a
100 g fat/day diet.
Reduce dietary fat to < 25 g/meal.
Supplementation of fat-soluble vitamins may be indicated.

Lipase, oral, equivalent to lipase 30 000 units per day, in divided doses
with meals.
Aim for symptom control and/or 5% of normal faecal fat output.
1.1.8 PEPTIC ULCER
K27
DESCRIPTION
Ulcer in the stomach mucosa (gastric ulcer: GU) or first few centimetres of
the duodenum (duodenal ulcer: DU), which penetrates into or through the
muscularis mucosa.
Diagnosis is made after endoscopy, as all GUs require biopsy to exclude
malignancy.
Patients with GUs and complicated DUs, those that have bled, perforated or
are recurrent, must be rescoped at appropriate intervals until the ulcer has
healed. H. pylori can be assessed at scope by rapid urease testing (RUT) or
biopsy.
GENERAL MEASURES
Advise patient to avoid ulcerogenic medications, e.g. NSAIDs.
Advise patient to stop smoking and drinking alcohol.
Dietary advice by dietician.
2015
1.5
CHAPTER 1
ALIMENTARY TRACT
MEDICINE TREATMENT
H. pylori +ve
The vast majority of GUs and DUs are associated with H. pylori infection and
eradication therapy is indicated if infection is present. This will greatly reduce
the rate of recurrent ulceration. Empiric eradication of H. pylori is not
recommended.
Proton pump inhibitor (PPI):

Lansoprazole, oral, 30 mg 12 hourly.
o Duodenal ulcer: for 7 days.
o Gastric ulcer: for 28 days.
vii
AND
H. pylori eradication:

Amoxicillin, oral, 1 g 12 hourly for 7 days.
OR
For severe penicillin allergy:

Azithromycin, oral, 500 mg daily for 3 days.
LoE:I
viii
LoE:I
AND

Metronidazole, oral, 400 mg 12 hourly for 7 days.
Failure of H. pylori eradication: Discuss with specialist.
H. pylori –ve
These are usually a consequence of NSAID use.
Stop NSAID until ulcer has healed.
If patient is unable to stop NSAID, refer to specialist.
Proton pump inhibitor (PPI):

Lansoprazole, oral, 60 mg daily.
o Duodenal ulcer: for 14 days.
o Gastric ulcer: for 28 days.
ix
LoE:II
Resistant disease
Ulcer not healing.
High-risk patients, i.e. poor surgical risk and the elderly or concomitant
disease. Maintenance therapy with PPI, e.g.:

Lansoprazole, oral, 30 mg daily. Specialist initiated.
x
LoE:III
2015
1.6
CHAPTER 1
ALIMENTARY TRACT
1.2 HEPATIC DISORDERS
1.2.1 HEPATITIS, NON-VIRAL
K70.1/K71/K75.4
* Notifiable if caused by agricultural chemicals or insecticides.
DESCRIPTION
Any form of hepatitis not caused by the common hepatotropic viruses.
Liver biopsy is indicated if hepatitis persists or diagnosis is unclear.
GENERAL MEASURES
Diet: restrict protein if features of liver failure are present. Excessive protein
restriction may accentuate catabolism.
Avoid alcohol.
Avoid other hepatotoxic agents.
Monitor blood glucose regularly because hypoglycaemia is common.
If the patient is bleeding, check INR and correct coagulopathy with:

FFP or lyophilised plasma.
xi
LoE:II
Routine administarion of parenteral vitamin K1 is of unproven value.
MEDICINE TREATMENT
Hepatitis due to infections
Antibiotic therapy based on culture.
Alcohol-induced hepatitis

Thiamine, oral, 100 mg daily
Other vitamins if indicated.
Drug-induced hepatitis
Stop all potentially hepatotoxic medication immediately, in consultation with
a specialist.
Auto-immune hepatitis
Patients with persistent hepatitis, negative viral markers and no
hepatotoxins. Biopsy and autoimmune markers are necessary to make the
diagnosis.
If autoimmune hepatitis:

Prednisone, oral, 0.5 mg/kg daily.
o Taper dose to a suitable maintenance dose. (Refer to page xxvii for
an example of a dose reduction regimen).
AND (on consultation with gastroenterologist or hepatologist)

Azathioprine, oral, 0.5 mg/kg daily, titrated up to 1 mg/kg daily
depending on response and WCC.
2015
1.7
CHAPTER 1
ALIMENTARY TRACT
REFERRAL
»
Where patients cannot be managed locally or biopsy cannot be done, i.e.
diagnosis is unclear.
» Non-resolving hepatitis.
Refer timeously before extensive liver damage occurrs.
1.2.2 ACUTE LIVER FAILURE
K72.9
DESCRIPTION
Acute liver failure refers to the development of severe acute liver injury with
encephalopathy and impaired synthetic function (INR of ≥1.5) in a patient
without cirrhosis or preexisting liver disease. There are many causes, but the
commonest are viral hepatitis, alcohol, drug-induced liver injury, or toxins.
GENERAL MEASURES
Patient education.
Avoid hepatotoxic drugs and alcohol.
Rest and reduce physical activity.
Protein restriction indicated for encephalopathy. Severe protein restriction
may accentuate catabolism. Use increments of 20 g protein per day as
tolerated.
Monitor blood glucose regularly because hypoglycaemia is common.
Correct electrolyte disturbances.
Exclude GI bleed as precipitant
Avoid any measure, e.g. medications that may worsen or precipitate
functional deterioration.
Avoid vigorous paracentesis.
Exclude infection as precipitant.
If the patient is bleeding, check INR and correct coagulopathy with FFP or
lyophilised plasma. Routine administarion of parenteral vitamin K 1 is of
unproven value.
MEDICINE TREATMENT

Lactulose, oral, 10–30 mL 8 hourly, titrated to attain 2–3 soft stools per
day.
Do not give antibiotics unless there is evidence of bacterial sepsis.
REFERRAL
All cases of severe acute liver failure should be discussed with a specialist.
2015
1.8
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ALIMENTARY TRACT
1.2.3 PORTAL HYPERTENSION AND CIRRHOSIS
K76.6
DESCRIPTION
The complications of portal hypertension are:
» variceal bleeds
» ascites and fluid overload
» encephalopathy
» spontaneous bacterial peritonitis in patients with ascites
GENERAL MEASURES
Ascites: sodium restriction, i.e. ≤ 2 g/day or ≤ 88 mmol/day.
Monitor weight regularly.
Bed rest.
Encephalopathy: low protein diet. Severe protein restriction may accentuate
catabolism. Use increments of 20 g protein per day as tolerated.
Exclude infection, high protein load, occult bleed, sedatives and electrolyte
disturbances.
Variceal bleeding: endoscopic sclerotherapy and/or banding.
MEDICINE TREATMENT
Ascites

Single morning dose of oral spironolactone, oral 100 mg and
furosemide, oral, 40 mg.
o Increase the dose by 100 and 40 mg, respectively, every 3–5 days,
to a maximum dose of 400 mg spironolactone and 160 mg of
furosemide.
o Rapid fluid shifts may precipitate acute liver and/or renal failure.
o Spironolactone may cause hyperkalaemia.
Monitoring of sodium, potassium and renal function is essential in patients
taking spironolactone. Avoid if eGFR < 30 mL/minute.
xii
LoE:III
Measure response to diuretics by weighing patient daily. Aim for maximal
weight loss of:
500 g/day
patients without oedema
1 000 g/day
patients with oedema
Tense ascites
Albumin replacement should be considered if > 5 L of fluid is removed:
xiii
LoE:II

Albumin, IV, 40 g (20%) , as an infusion.

Introduce diuretics and titrate doses as necessary to prevent recurrence
of ascites (see above).
2015
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ALIMENTARY TRACT
Note:
» Avoid NSAIDS and ACE-inhibitors.
» Exclude spontaneous bacterial peritonitis in patients with new onset
ascites.
Refractory ascites
» No response to optimal diuretic therapy, despite sufficient sodium
restriction (≤ 2 g/day or ≤ 88 mmol/day) with avoidance of NSAIDs.
» Ascites recurs rapidly following therapeutic paracentesis.
Perform serial large volume paracentesis, as an outpatient, usually not more
frequently than every 2 weeks.
Haemodynamic collapse is more likely in patients who are intravascularly
volume depleted. Check renal function before paracentesis.
Albumin replacement should be considered if > 5 L of fluid is removed:
xiv
LoE:II

Albumin, IV, 40 g (20%) , as an infusion.
Encephalopathy

Lactulose, oral, 10–30 mL 8 hourly, depending on stool number and
consistency (aim for 2 soft stools/day).
Look for preciptating factors : Sepsis, protein load, GIT bleed, overdiuresis,
sedation
Oesophageal varices
To reduce the risk of bleeding:

Carvedilol, oral, 12.5 mg 12 hourly for patients with Child Pugh A and
xv
6.25 mg 12 hourly for Child Pugh B and C. Monitor pulse
LoE:II
and BP.
1.2.4 HEPATITIS, VIRAL
B19.9
* Notifiable disease
DESCRIPTION
Hepatitis caused by one of the hepatotropic viruses, hepatitis A, B, C and E.
1.2.4.1 HEPATITIS B, ACUTE
B16.9
GENERAL MEASURES
Bed-rest until acute phase is over.
Avoid alcohol during the illness and for ≥ 6 months after clinical recovery.
Screen sexual contacts of patients with acute hepatitis B. If they are nonimmune (negative for hepatitis B antibodies) then they should receive
hepatitis B active immunisation.
2015
1.10
CHAPTER 1
ALIMENTARY TRACT
MEDICINE TREATMENT
For nausea and vomiting:

Metoclopramide, IV/oral, 10 mg 8 hourly as required.
Hepatitis B virus: prophylaxis following exposure e.g. needle stick injury
Persons at risk can be protected by passive immunisation with hyper
immune serum globulin prepared from blood containing anti-HBs.
It is essential that all categories of healthcare workers (HCW) who are at risk
of exposure, including cleaning staff, be fully vaccinated against hepatitis B.
All exposure incidents must be adequately documented for possible
subsequent compensation.
Recommended post-exposure management for HCW exposed to infectious
material from patients with infectious hepatitis B (either surface antigen or e
antigen positive).
HBsAg: hepatitis B surface antigen
HBIG: hepatitis B immune globulin
Vaccination status
and antibody
response status of
HCW
Unvaccinated
OR
vaccination
incomplete
Vaccinated
AND HBsAb
> 10 units/mL#
Vaccinated
AND HBsAb
< 10 units/mL
HBsAb: hepatitis B surface antibody
Source patient status & treatment
HBsAg positive
HBsAg negative HBsAg unknown

HBIG, IM, 500
units*
Hep B vaccine
(3 doses at monthly
intervals)
No treatment
Initiate Hep B
 HBIG, IM, 500
vaccination
units*
(month 0, 1 and 6) Hep B vaccine
(3 doses at monthly
intervals)
No treatment
No treatment

Initiate Hep B
HBIG, IM, 500
 HBIG, IM, 500
vaccination
units *
units*
(month 0, 1 and 6) Repeat Hep B vaccine
Repeat Hep B
vaccine
(3 doses at monthly
(3 doses at monthly
intervals)
intervals)
* HBIG and first dose of vaccine to be given simultaneously, but at different sites.
#
If the delay in obtaining HBsAb results is more than 24 hours initiate treatment as for
vaccinated AND HBsAb < 10 units/mL.
1.2.4.2 HEPATITIS B, CHRONIC (NON-HIV COINFECTION)
B18.0/B18.1/B19.1
DESCRIPTION
The hepatitis B virus (HBV) is commonly transmitted via sexual transmission,
exposure to blood and other infectious body fluids, and vertically.
Acute infection may be asymptomatic or present as acute hepatitis. A
proportion of patients develop chronic hepatitis (defined as abnormalities
listed in the table below persisting for >6 months), which can result in
2015
1.11
CHAPTER 1
ALIMENTARY TRACT
cirrhosis and hepatocellular carcinoma.
It is essential to know the HIV status of all patients with chronic hepatitis B
before considering therapy.
Note that antiviral therapy is not indicated for acute hepatitis B infection.
There are 5 potential phases of chronic hepatitis B infection which determine
the need for treatment:
Phase
1. Immune
control
Serology
HBsAg positive
HBeAg negative
Viral
load
(HBV
DNA)
IU/mL
<2000
ALT
Normal
Management
» Treatment not
»
2. Immune
tolerant
HBsAg positive
HBeAg positive
>20000
(usually
>200000)
Normal
»
»
3. Immune
clearance
4. Immune
escape
5. Occult
hepatitis B
HBsAg positive
HBeAg positive
HBsAg positive
HBeAg negative
HBsAg negative
HBsAb negative
HB IgG core Ab
positive
routinely needed, but
should be followed
up.
Treat only if on
immunosuppressive
therapy to prevent
hepatitis B flares.
Treatment not
routinely needed, but
should be followed
up.
Treat only if on
immunosuppressive
therapy to prevent
hepatitis B flares.
Treatment required.
>20000
Elevated
»
>2000
Elevated
» Treatment required.
<200
-
» No follow-up
required.
» Treat only if on
immunosuppressive
therapy to prevent
hepatitis B flares.
Treat all patients with cirrhosis regardless of ALT level, HBeAg status and
DNA level, to prevent hepatitis B flares that will lead to decompensation.
MEDICINE TREATMENT

Tenofovir, oral, 300 mg daily, if estimated CrCl greater than 50 ml/min.
xvi
LoE:III
AIMS OF TREATMENT
HBeAg-positive disease
» Sustained HBsAg loss due to therapy, with/without the development of
anti-HBs, and
» Suppression of HBV DNA <2000 or undetectable levels, and
2015
1.12
CHAPTER 1
»
»
ALIMENTARY TRACT
Normalisation of ALT, and
HBeAg loss and seroconversion to anti-HBe.
HBeAg-negative disease
» Sustained HBsAg loss off therapy, with/without the development of antiHBs, and
» Suppression of HBV DNA <2000 or undetectable levels, and
» Normalisation of ALT.
MONITORING WHILST ON TENOFOVIR
Weeks 1 and 4 and every 12 weeks
ALT, INR
At inititiation of TDF, then at 3, 6 and Serum creatinine
12 months after initiation and every
12 months thereafter if on TDF
Every 6 months
HBeAg-positive patients: HBeAg/
anti-HBe, HbsAg after anti-HBe
seroconversion
In HBeAg-positive patients: 12
months after HBeAg seroconversion
HBeAg-negative patients: HBsAg
with persistently undetectable HBV
DNA.
HBV DNA levels
Adapted from: Spearman CW, Sonderup MW, Botha JF, van der Merwe SW, Song E, Kassianides C, Newton KA,
Hairwadzi HN. South African guideline for the management of chronic hepatitis B: 2013. S Afr Med J. 2013
May;103(5 Pt 2):337-49. http://www.ncbi.nlm.nih.gov/pubmed/23967497
DISCONTINUE TREATMENT WITH TENOFOVIR WHEN:
» HBeAg-positive patients: 12 months after HBeAg seroconversion and
in association with persistently normal ALT levels and undetectable HBV
DNA levels.
» HBeAg-negative patients: Longterm therapy unless HBsAg
seroconversion is achieved.
» Cirrhotic patients: Lifelong treatment.
REFERRAL
Failure of or contraindications to tenofovir.
1.2.4.3 HEPATITIS B, CHRONIC (HIV COINFECTION)
B18.0/B18.1/B19.1 and B20
See chapter 10: HIV and AIDS.
2015
1.13
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ALIMENTARY TRACT
1.2.5 LIVER ABSCESS, PYOGENIC
K75.0
DESCRIPTION
Focal bacterial infection, usually polymicrobial, of the liver with pus. Multiple
abscesses are not uncommon.
GENERAL MEASURES
Drainage is essential in all cases. This should preferably be done
percutaneously by inserting a catheter under ultrasound guidance.
MEDICINE TREATMENT
Empiric antibiotic therapy

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
If unable to tolerate oral therapy:

Amoxicillin/clavulanic acid, IV, 1000/200 mg 8 hourly.
Duration of antibiotic therapy is ill-defined, but may need to be for as long as
12 weeks in cases of multiple abscesses. Continue until drainage is
complete and CRP has returned to normal values. Ultrasound resolution is
very slow and is not useful for monitoring response to therapy.
1.2.6 LIVER ABSCESS, AMOEBIC
A06.4
DESCRIPTION
Focal hepatic infection due to E. histolytica. Only about a third of cases have
concomitant amoebic colitis. Diagnosis can be excluded if the serological test
is negative. It is essential to exclude pyogenic infection (a diagnostic aspirate
should be taken under ultrasound guidance in all cases where there is doubt).
GENERAL MEASURES
Drainage is recommended for abscesses that are large, i.e. >10 cm
diameter, involve the left lobe or are near the surface of the liver. Drainage
can be achieved by percutaneous aspiration under ultrasound guidance.
MEDICINE TREATMENT

xvii
LoE:III
Metronidazole, oral, 800 mg 8 hourly for 10 days.
1.2.7 ACUTE
CHOLECYSTITIS
CHOLANGITIS
AND
ACUTE
K81.0/K83.0
GENERAL MEASURES
Surgical drainage / cholecystectomy according to indication and/or patient's
condition.
2015
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CHAPTER 1
ALIMENTARY TRACT
MEDICINE TREATMENT
Acute cholecystitis
Mild and asymptomatic cases without risk factors may not require antibiotic
treatment. If signs of infection present and/or risk factors for severe disease
present:
» Elderly patients (older than 60 years of age)
» Co-morbidity
» Immune compromise
Acute cholecystitis and acute cholangitis
 Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
If unable to tolerate oral therapy:
 Amoxicillin/clavulanic acid, IV, 1000/200 mg 8 hourly.
REFERRAL
»
»
»
Clinical deterioration or failure to improve.
Fistulae or perforation.
Need for complicated surgery.
1.3 DIARRHOEA
1.3.1 CHOLERA
A00.9
*This is a notifiable disease.
DESCRIPTION
Diarrhoea due to Vibrio cholerae, often in outbreaks.
GENERAL MEASURES
Rehydration is the cornerstone of management. This should be done with
oral rehydration solution (ORS) unless the patient is vomiting or profoundly
dehydrated.
MEDICINE TREATMENT

Ciprofloxacin, oral, 1 g immediately as a single dose.
o Adjust antibiotic choice, according to the sensitivity of the isolate
responsible for the local epidemic.
1.3.2
ACUTE
INFLAMMATORY
(DYSENTERY)
DIARRHOEA
A03.9
DESCRIPTION
Diarrhoea with neutrophils, blood and/or mucus.
2015
1.15
CHAPTER 1
ALIMENTARY TRACT
GENERAL MEASURES
Rehydration is the cornerstone of management. This should be done with
oral rehydration solution (ORS) unless the patient is vomiting or profoundly
dehydrated.
Stool culture is advised.
MEDICINE TREATMENT
Loperamide is contraindicated as it may result in toxic megacolon.
Antibiotic therapy
Consider in patients with signs of sepsis and severe cases or significant
underlying disease:

Ceftriaxone, IV 1g daily.
o Switch to oral therapy when clinically appropriate i.e. ciprofloxacin
500mg 12 hourly.
For uncomplicated dysentry in patients with no co-morbidity:

Ciprofloxacin, oral, 500 mg 12 hourly for 3 days.
For uncomplicated dysentry in patients with significant co-morbidity e.g.
immunocompromised patients:

Ciprofloxacin, oral, 500 mg 12 hourly for 7 days.
REFERRAL
Persistent diarrhoea with blood and mucus for longer than 2 weeks.
1.3.3 DIARRHOEA, ACUTE NON-INFLAMMATORY
A04.1
DESCRIPTION
Diarrhoea without macroscopic blood or mucus, or neutrophils on microscopy.
Common causes include viruses and enterotoxigenic strains of E. coli.
Note: Neutropenic patients may have inflammatory diarrhoea in the absence
of neutrophils.
GENERAL MEASURES
Rehydration is the cornerstone of management. This should be done with
oral rehydration solution (ORS) unless the patient is vomiting or profoundly
dehydrated.
MEDICINE TREATMENT

Loperamide, oral, 4 mg immediately, followed by 2 mg after each loose
stool.
o Maximum dose: 16 mg daily.
2015
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ALIMENTARY TRACT
1.3.4 DIARRHOEA, ANTIBIOTIC-ASSOCIATED
A04.7
DESCRIPTION
Diarrhoea caused by altered bowel flora due to antibiotic exposure.
Clostridium difficile infection may result in severe disease and/or the
development of pseudomembranous colitis. Diagnosis is confirmed in the
laboratory on a stool sample.
GENERAL MEASURES
The most important aspect of management is discontinuing antibiotics.
Rehydration may be necessary. This should be done with oral rehydration
solution (ORS) unless the patient is vomiting or profoundly dehydrated.
Surgery for bowel perforation.
MEDICINE TREATMENT
Loperamide is contraindicated as it may result in toxic megacolon.
If diarrhoea does not settle on antibiotic withdrawal or if pseudomembranous
colitis is present:
xviii
LoE:I

Metronidazole, oral, 400 mg 8 hourly for 10 days.
Failure to respond to metronidazole after 5 days - consult a specialist and:
xix
ADD
LoE:III

Vancomycin, oral, 125 mg 6 hourly. (Give the parenteral
formulation orally).
xx
LoE:I
1.3.5 AMOEBIC DYSENTERY
A06
DESCRIPTION
Diarrhoea with blood and/or mucus due to E. histolytica. Organism must be
demonstrated on a warm stool specimen for microscopy.
GENERAL MEASURES
Rehydration may be necessary. This should be done with oral rehydration
solution (ORS) unless the patient is vomiting or profoundly dehydrated.
Surgery for bowel perforation.
MEDICINE TREATMENT
Loperamide is contraindicated as it may result in toxic megacolon.
2015
1.17
CHAPTER 1

ALIMENTARY TRACT
Metronidazole, oral, 800 mg 8 hourly for 10 days.
xxi
LoE:III
1.3.6 GIARDIASIS
A07.1
DESCRIPTION
Infection with the protozoan parasite, G. lamblia which colonises the
proximal small intestine. Does not typically presents with acute diarrhoea.
GENERAL MEASURES
Fluid and electrolyte replacement in severe diarrhoea.
MEDICINE TREATMENT

Metronidazole, oral, 2 g daily for 3 days.
1.3.7 TYPHOID
A01.0
See section 9.9: Typhoid fever.
1.3.8 BACTERIAL PERITONITIS
K65
DESCRIPTION
Infection of the peritoneum, usually secondary to a surgical cause such as
perforated bowel. In this setting polymicrobial infection with anaerobes,
Gram positive cocci, and Enterobacteriaceae are usually found.
Primary or spontaneous bacterial peritonitis is much less common and
usually complicates ascites in patients with portal hypertension. This is not
usually polymicrobial but due generally to Enterobacteriaceae such as E.
coli. Spontaneous bacterial peritonitis is often culture-negative but is
9
3
diagnosed by ascitic neutrophil count >0.25 x 10 /L (250 cells/mm ).
GENERAL MEASURES
Secondary peritonitis
Intravenous fluids and nasogastric suction.
Prompt surgical intervention is essential.
MEDICINE TREATMENT
Empiric antibiotic therapy
For surgical causes of peritonitis:

Amoxicillin/clavulanic acid, IV 1.2 g 8 hourly.
As soon as patient can tolerate oral medication:
 Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
2015
1.18
CHAPTER 1
ALIMENTARY TRACT
For spontaneous bacterial peritonitis:

Ceftriaxone, IV, 1 g daily.
o Patients not responding to ceftriaxone after 48 hours, consult a
specialist.
Switch to oral therapy when clinically appropriate according to culture or
treat with:

Ciprofloxacin, oral, 500 mg 12 hourly.
o Total duration of therapy: 14 days.
References:
i
Polyethylene glycol, oral: Park DI, Park SH, Lee SK, Baek YH, Han DS, Eun CS, Kim WH, Byeon JS, Yang SK.
Efficacy of prepackaged, low residual test meals with 4L polyethylene glycol versus a clear liquid diet with 4L
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Sodium sulfate, oral: Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ,
Boland CR, Giardello FM, Lieberman DA, Levin TR, Rex DK. Optimizing adequacy of bowel cleansing for
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Polyethylene glycol, oral/ sodium sulfate, oral (split dosing): Bucci C, Rotondano G, Hassan C, Rea M, Bianco
MA, Cipolletta L, Ciacci C, Marmo R. Optimal bowel cleansing for colonoscopy: split the dose! A series of metaanalyses of controlled studies. Gastrointest Endosc. 2014 Oct;80(4):566-576.e2.
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iii
Adjunctive agents: American Society of Colon and Rectal Surgeons (ASCRS); American Society for
Gastrointestinal Endoscopy (ASGE); Society of American Gastrointestinal and Endoscopic Surgeons (SAGES),
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colonoscopy. Am Clin Res 1987;19:34-8. http://www.ncbi.nlm.nih.gov/pubmed/3555277
iv
Amoxicillin/clavulanic acid, oral/IV (severe disease): South African Antibiotic Stewardship Programme. A
Pocket Guide to Antibiotic Prescribing for Adults in South Africa, 2015.
http://www.fidssa.co.za/images/SAASP_Antibiotic_Gudidelines_2015.pdf
v
Lansoprazole, oral: Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME. Short-term treatment with
proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like
symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2013 May 31;5:CD002095.
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vi
Amoxicillin/clavulanic acid, IV (abscess of the pancreas): South African Antibiotic Stewardship Programme. A
Pocket Guide to Antibiotic Prescribing for Adults in South Africa, 2015.
http://www.fidssa.co.za/images/SAASP_Antibiotic_Gudidelines_2015.pdf
vii
Lansoprazole, oral (H.pylori +ve): Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor therapy for
peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials. Mayo Clin Proc. 2007
Mar;82(3):286-96. http://www.ncbi.nlm.nih.gov/pubmed/17352364
Lansoprazole, oral (H.pylori +ve): Neumann I, Letelier LM, Rada G, Claro JC, Martin J, Howden CW, Yuan Y,
Leontiadis GI. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane
Database Syst Rev. 2013 Jun 12;6:CD007999. http://www.ncbi.nlm.nih.gov/pubmed/23760821
Lansoprazole, oral (H.pylori +ve): SAMF, 2014.
Lansoprazole, oral (H.pylori +ve): Contract circlar HP09-2014SD. http://health.gov.za/
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ALIMENTARY TRACT
viii
Azithromycin: Dong J, Yu XF, Zou J. Azithromycin-containing versus standard triple therapy for Helicobacter
pylori eradication: a meta-analysis. World J Gastroenterol. 2009 Dec 28;15(48):6102-10.
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Azithromycin: National Department of Health. Essential Drugs Programme. Medicine review: The efficacy of
Azithromycin compared to Clarithromycin in the treatment of H.Pylori infection, 26 November 2015.
http://health.gov.za/
ix
Lansoprazole, oral (H.pylori +ve): Contract circlar HP09-2014SD. http://health.gov.za/
Lansoprazole, oral (H.pylori +ve): Avner DL, Movva R, Nelson KJ, McFarland M, Berry W, Erfling W.
Comparison of once daily doses of lansoprazole (15, 30, and 60 mg) and placebo in patients with gastric ulcer. Am
J Gastroenterol. 1995 Aug;90(8):1289-94. http://www.ncbi.nlm.nih.gov/pubmed/7639232
x
Lansoprazole, oral (Resistant ulcer): Contract circlar HP09-2014SD. http://health.gov.za/
Lansoprazole, oral (Resistant ulcer): SAMF, 2014
xi
Fresh frozen plasma/ Lyophilised plasme: Williamson LM, Llewelyn CA, Fisher NC, Allain JP, Bellamy MC,
Baglin TP, Freeman J, Klinck JR, Ala FA, Smith N, Neuberger J, Wreghitt TG. A randomized trial of
solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver
transplantation. Transfusion. 1999 Nov-Dec;39(11-12):1227-34. http://www.ncbi.nlm.nih.gov/pubmed/10604250
xii
Spironolactone: Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with
ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107.
http://www.ncbi.nlm.nih.gov/pubmed/19475696
Spironolactone: SAMF, 2014.
Furosemide: Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites
due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107. http://www.ncbi.nlm.nih.gov/pubmed/19475696
xiii
Albumin, IV: AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis:
an update. Hepatology. 2009 Jun;49(6):2087-107. http://www.ncbi.nlm.nih.gov/pubmed/19475696
Albumin, IV: Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing largevolume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81.
http://www.ncbi.nlm.nih.gov/pubmed/22095893
xiv
Albumin, IV: AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis:
an update. Hepatology. 2009 Jun;49(6):2087-107. http://www.ncbi.nlm.nih.gov/pubmed/19475696
Albumin, IV: Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing largevolume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81.
http://www.ncbi.nlm.nih.gov/pubmed/22095893
xv
Carvedilol: Aguilar-Olivos N, Motola-Kuba M, Candia R, Arrese M, Méndez-Sánchez N, Uribe
M, Chávez-Tapia NC. Hemodynamic effect of carvedilol vs. propranolol in cirrhotic patients: Systematic review and
meta-analysis. Ann Hepatol. 2014 Jul-Aug;13(4):420-8. http://www.ncbi.nlm.nih.gov/pubmed/24927613
xvi
Tenofovir: Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G,
Flaherty JF, Schall RA, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression
of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow up
study. Lancet. 2013;381:468–75. http://www.ncbi.nlm.nih.gov/pubmed/23234725
Tenofovir: World Health Organisation. Guidelines for the prevention, care and treatment of persons with chronic
hepatitis B infection, March 2015. http://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/
xvii
Metronidazole, oral: Ravdin JI. Amebiasis. Clin Infect Dis. 1995 Jun;20(6):1453-64; quiz 1465-6.
Review. http://www.ncbi.nlm.nih.gov/pubmed/7548493
Metronidazole, oral: Wuerz T, Kane JB, Boggild AK, Krajden S, Keystone JS, Fuksa M, Kain KC, Warren R,
Kempston J, Anderson J. A review of amoebic liver abscess for clinicians in a nonendemic setting. Can J
Gastroenterol. 2012 Oct;26(10):729-33. http://www.ncbi.nlm.nih.gov/pubmed/23061067
xviii
Metronidazole, oral: Nelson RL, Kelsey P, Leeman H, Meardon N, Patel H, Paul K, Rees R, Taylor B, Wood E,
Malakun R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev.
2011 Sep 7;(9):CD004610. http://www.ncbi.nlm.nih.gov/pubmed/21901692
xix
Metronidazole, oral (monitoring for failure to respond): Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan
AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and
prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; quiz 499.
http://www.ncbi.nlm.nih.gov/pubmed/23439232
xx
Vancomycin, oral (parenteral formulation, given orally): Nelson RL, Kelsey P, Leeman H, Meardon N, Patel H,
Paul K, Rees R, Taylor B, Wood E, Malakun R. Antibiotic treatment for Clostridium difficile-associated diarrhea in
adults. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD004610. http://www.ncbi.nlm.nih.gov/pubmed/21901692
xxi
Metronidazole, oral: Marie C, Petri WA Jr. Amoebic dysentery. BMJ Clin Evid. 2013 Aug 30;2013. pii:
0918. http://www.ncbi.nlm.nih.gov/pubmed/23991750
Metronidazole, oral: Gonzales ML, Dans LF, Martinez EG. Antiamoebic drugs for treating amoebic colitis.
Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006085. http://www.ncbi.nlm.nih.gov/pubmed/19370624
2015
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BLOOD AND BLOOD FORMING ORGANS
2.1 ANAEMIA
Defined as a reduction in the absolute number of circulating red blood cells
and most commonly diagnosed when the haemoglobin (Hb) concentration is
reduced below the reference range for age and gender. The clinical features
depend on the severity of anaemia, the rate at which it developed and the
oxygen demands of the patient.
Cause
Can be classified according to the mean corpuscular volume (MCV) of the
red blood cell (RBC) into macrocytic anaemia (MCV>100 fL); microcytic
anaemia (MCV < 80) or normocytic anaemia (MCV 80 - 100 fL).
2.2 ANAEMIA, IRON DEFICIENCY
D50.9
DESCRIPTION
Anaemia due to iron deficiency. Common causes of iron deficiency are
chronic blood loss or poor nutritional intake.
Investigations
» Low MCV and MCH (mean cell Hb – hypochromia).
» FBC Smear: Hypochromic microcytic anaemia and pencil cells often
reported.
» Confirm with low ferritin.
» Investigate for cause of iron deficiency.
» Consider upper and lower endoscopies in high risk patients (all males
and postmenopausal female patients) and patients not responding to
treatment.
GENERAL MEASURES
Identify and treat the underlying cause.
Dietary adjustment if this is the underlying cause.
MEDICINE TREATMENT
Oral iron supplementation
Treatment
Treat underlying cause.

Ferrous sulphate compound BPC, oral, 170 mg (± 65 mg elemental
iron), 12 hourly.
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o
o
Do not ingest with tea, antacids or calcium supplements/milk.
Doses should be taken on an empty stomach, but if gastrointestinal
side effects occur doses should be taken with meals.
o Continue with treatment for 3 months once Hb has normalised to
replace iron stores.
i
LoE:III
Follow the patient after one month of treatment and Hb
should rise by at least 2 g/dl in the adherent patient without ongoing blood
loss.
Prophylaxis
For example during pregnancy:

Ferrous sulphate compound BPC, oral, 170 mg (± 65 mg
elemental iron), 12 hourly.
ii
LoE:III
Consider the following if there is failure to respond to iron therapy:
» non-adherence,
» continued blood loss,
» wrong diagnosis
» malabsorption, and
» mixed deficiency; concurrent folate or vitamin B12 deficiency.
Parenteral iron
Parenteral iron is seldom required and may be associated with anaphylaxis.
Parenteral iron is only indicated when oral iron is:
» expected to be ineffective, e.g. malabsorption, patients on
haemodialysis and erythropoietin therapy, or
» not tolerated.
In people who require repeated therapy, the intravenous route is preferred.
Minimum required dose is 250 mg of iron per gram of Hb below normal.
Use in consultation with a specialist.

Iron, IV.
o An initial total dose of 600 mg intravenous iron is usually adequate
to raise the Hb.
OR
For patients requiring a single dose:

Low molecular weight iron dextran.
o Determine total dose of iron required (total dose should not exceed
20 mg/kg body weight).
o Start with test dose: 25 mg in 100 ml sodium chloride 0.9%, infused
over 15 minutes and observe the patient for 1 hour.
o If there is no adverse drug reaction, administer the remaining dose
in 500 mL of sodium chloride 0.9%, 0.9% over 4-6 hours.Observe
the patient for 1 hour after the infusion.
iii
LoE:III
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Resuscitation equipment should be ready to manage anaphylaxis.
Red cell concentrate transfusion
Indicated in patients with:
» anaemia leading to cardiac failure or severe dyspnoea;
» active, ongoing bleeding; or
» where correction of anaemia is required prior to performing an urgent
invasive procedure or surgery.
2.3 ANAEMIA, MEGALOBLASTIC
D53.1
DESCRIPTION
Anaemia caused by a deficiency of folate and/or vitamin B 12.
Note that several medicines can cause macrocytic anaemia (e.g.
hydroxyurea, stavudine and zidovudine) without deficiencies of folate and/or
vitamin B12.
Investigations
» Elevated MCV (mean corpuscular volume) and MCH (mean corpuscular
haemoglobin).
» Pancytopaenia in severe cases.
» Full blood count smear: oval macrocytes, hypersegmentation of
neutrophils, thrombocytopenia with giant platelets.
» Decreased serum vitamin B12 or red blood cell folate.
» Intrinsic factor antibodies, and/ or anti-parietal cell antibodies are found
in pernicious anaemia.
GENERAL MEASURES
Dietary modifications to ensure adequate intake of folate and vitamin B12
(important in vegetarians and malnourished patients).
Identify and treat the underlying cause, e.g. antibiotics for intestinal
overgrowth with bacteria.
Metformin use can lead to vitamin B12 deficiency by interfering with
absorption.
MEDICINE TREATMENT
After blood samples for RBC, folate and vitamin B12 levels have been taken,
start with folic acid and vitamin B12 supplementation.
Monitor serum potassium and replace if necessary.
Give vitamin B12 and folic acid together until the test results are available
as giving folic acid alone in patients with a B12 deficiency may precipitate
a permanent neurological deficit.
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CHAPTER 2
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Adjust management according to results.
Folic acid deficiency

Folic acid, oral, 5 mg daily until haemoglobin returns to normal.
Prolonged treatment may be required for malabsorption states.
Vitamin B12 deficiency

Vitamin B12, IM.
o 1 mg daily for 5 days, then weekly for a further 3 doses
o Follow with 1 mg every second month for life in patients with
pernicious anaemia.
Note:
» Response to treatment is associated with an increase in strength and
improved sense of well-being.
» Reticulocytosis begins 3–5 days after therapy and peaks at about day 7.
» The anaemia normally corrects within 1–2 months. The white cell count
and platelets normalise in 7–10 days. As there is an increase in red
blood cell production, iron and folic acid supplementation is also
recommended, until Hb has normalised. Check for hypokalaemia in the
first few days of therapy.
Hypokalaemia: See section 7.2.2: Hypokalaemia.
Consider the following if there is failure to respond:
» Co-existing folate and/or iron deficiency,
» Other causes of macrocytosis:
- Myelodysplasia,
- Hypothyroidism,
- Chronic alcohol use,
» Drug-induced, e.g. hydroxyurea, stavudine and zidovudine.
Prophylaxis
Vitamin B12 is indicated for patients after total gastrectomy or ileal resection.

Vitamin B12, IM, 1 mg every second month for life.
Indications for folic acid:
» Chronic inherited haemolytic anaemias, e.g. sickle cell anaemia,
thalassaemia.
» Myeloproliferative disorders.
» Exfoliative skin disorders.
» Increased demands, e.g. pregnancy, chronic haemodialysis.

Folic acid, oral, 5 mg daily.
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2.4 ANAEMIA, CHRONIC DISORDER
D63
DESCRIPTION
Anaemia due to chronic inflammation. This is characteristically a
normochromic normocytic anaemia. Common causes of anaemia of chronic
disorder include:
» malignancy, e.g. haematological or solid tumours,
» autoimmune disorders, e.g. rheumatoid arthritis,
» chronic infections, e.g. HIV and TB,
» chronic kidney disease
TREATMENT
Treat the underlying condition.
Transfusion is seldom necessary.
Do not treat with iron, folic acid or vitamin B 12 unless there is a documented
deficiency (note that diagnosing iron deficiency is difficult in chronic
disorders as ferritin increases and serum iron decreases due to the acute
phase response).
2.5 ANAEMIA, HAEMOLYTIC
D59
DESCRIPTION
Anaemia due to destruction of red blood cells. Destruction may be due to:
» Extracellular factors such as auto-immunity or mechanical factors, e.g.
disseminated intravascular coagulation (DIC), hypersplenism,
mechanical heart valves.
» Abnormalities of the cell membrane, e.g. hereditary spherocytosis.
» Enzymes, e.g. G6PD deficiency.
» Haemoglobin abnormalities, e.g. sickle cell anaemia, thalassaemia.
Investigations
» Evidence of haemolysis: anaemia, reticulocytosis, decreased
haptoglobin, increased lactate dehydrogenase (LDH) and unconjugated
hyperbilirubinaemia.
» Full Blood count smear: Spherocytes often reported
» Coombs’ test (direct antiglobulin) is usually positive with autoimmune
haemolysis.
» HIV status.
GENERAL MEASURES
Treat the underlying cause.
Do not transfuse prior to appropriate investigations, unless anaemia is severe.
Coombs-positive haemolytic anaemia may be technically difficult to cross
match.
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Efficacy of transfusion is limited by the shortened red cell survival due to
haemolysis.
In G6PD deficiency, avoid drugs known to cause haemolysis, including
aspirin, sulphonamides (including cotrimoxazole), dapsone and primaquine.
In patients with cold agglutinins all transfusions must be given through a
blood warmer to avoid cold-induced haemolysis.
MEDICINE TREATMENT
All patients:
Because of high red cell turnover, supplement with:

Folic acid, oral, 5 mg daily.
Autoimmune haemolytic anaemia
Treat under specialist supervision.

Prednisone, oral.
o Initial dose:1 mg/kg daily, until Hb stable and >10 g/dL.
iv
o Taper slowly and monitor Hb at least once weekly.
LoE:III
(Refer to page xxvii for an example of a dose
reduction regimen).
o Glucocorticoids can be stopped when there is normalization of the
haemoglobin and LDH. The patient should be monitored for
recurrence following cessation of treatment.
REFERRAL/CONSULTATION
If inadequate response:
» haemolysis remains severe for 3 weeks at prednisone doses of 1 mg/kg,
if remission cannot be maintained on low doses of prednisone, or if the
patient has intolerable adverse effects or contraindications to
glucocorticoids.
Refer to specialist for second-line treatment:
» Splenectomy: vaccination: see chapter 11: Surgical prophylaxis.
Immunosuppresive therapy is needed in some cases, initiated by specialists.
v
LoE:III
2.6 ANAEMIA, APLASTIC
D61.9
DESCRIPTION
Pancytopenia due to a hypoplastic bone marrow.
Clinical features:
» pallor
» purpura
» petechiae
» bleeding
» frequent or severe infections
2015
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MEDICINE TREATMENT
If neutropenic and febrile, see section 2.8: Febrile neutropenia.
REFERRAL
Discuss all cases of suspected aplastic anaemia with a specialist. (Stabilise
patient, if necessary, with blood products before transport but after
consultation with an expert).
Pancytopenia in HIV positive patients:
Full blood count (FBC) indicate different
thrombocytopaenia and leucopaenia.
degrees
of:
anaemia,
Most common causes include:
Direct effect of HIV, medication, secondary opportunistic infections,
malignancies and nutritional deficiencies.
Investigations
» Full blood count smear.
» vitamin B12 and red cell folate.
» Appropriate investigation to exclude opportunistic infections.
» Bone marrow trephine and aspiration in selected patients (where no
other cause is found, in patients with persistence pancytopaenia) to
exclude infiltration with opportunistic infections, malignancies, etc.
2.7 ANAEMIA, SICKLE CELL
D57
DESCRIPTION
Homozygous sickle cell anaemia (HbSS). Individuals with sickle cell trait
have < 50% HbS and are generally asymptomatic. Milder sickle cell disease
occurs in individuals with HbSC.
The disease is characterised by recurrent acute vaso-occlusive episodes
(“sickle crises”) and chronic haemolytic anaemia.
Adults develop hyposplenism, predisposing them to infection with
encapsulated bacteria.
Vaso-occlusive episodes
Vaso-occlusion can involve any part of the body, especially the skeleton.
Episodes may be triggered by dehydration, infection, stress or menstruation.
The most common presentation is with acute episodes of pain, varying in
severity, in the affected areas.
Investigations
The diagnosis is suspected from the history, peripheral blood examination,
and/or screening tests for sickling.
Diagnosis is confirmed on haemoglobin electrophoresis.
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GENERAL MEASURES (SEVERE VASO-OCCLUSIVE EPISODES)
Keep well hydrated with intravenous fluids.
Transfusion is only indicated for severe episodes with severe anaemia –
discuss with a specialist.
Pain must be controlled.
MEDICINE TREATMENT (SEVERE VASO-OCCLUSIVE EPISODES)

Use of Oxygen to maintain adequate saturation.
To prevent venous thromboembolism:

Unfractionated heparin, SC, 5000 IU 12 hourly.
OR

Low molecular weight heparin, e.g.:

Enoxaparin, SC, 40 mg daily.
vi
LoE:I
Analgesia
Refer to chapter 12: Anaesthesiology, pain and intensive care.
GENERAL MEASURES (CHRONIC MANAGEMENT)
Transfusion for severe anaemia should always be discussed with a
specialist.
MEDICINE TREATMENT (CHRONIC MANAGEMENT)
All patients:

Folic acid, oral, 5 mg daily.

Vaccination against infections due to pneumococci and haemophilus
(see section 9.2: Adult vaccination).
Hydroxyurea (specialist-initiated) is the mainstay of therapy in severe
disease. Typical indications include:
- frequent painful vaso-occlusive episodes,
- severe vaso-occlusive episodes (e.g. acute chest syndrome,
stroke), and
- severe symptomatic anemia.
REFERRAL
»
»
All patients, for chronic management in a specialised centre.
Vaso-occlusive episodes should be managed in consultation with a
specialist.
2.8 FEBRILE NEUTROPENIA
D70
DESCRIPTION
Febrile neutropenia is conventionally defined as an absolute neutrophil count
2015
2.8
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
9
of < 0.5 x 10 /L with a temperature of greater than 38°C for > 1 hour or a
single temperature of 38.3°C, but any neutropaenic patient showing clinical
signs of sepsis should be investigated.
This is a medical emergency as these patients can rapidly develop features
of severe sepsis (multi-organ failure and/or hypotension).
GENERAL MEASURES
Treat the underlying cause of neutropenia, if applicable.
Withdraw any medication that may cause neutropenia.
Consider removing central IV line.
Take blood and other relevant cultures before starting antimicrobial therapy.
Once culture results are available, adjust treatment to the most appropriate
narrow spectrum agent.
MEDICINE TREATMENT
For patients with febrile neutropenia within 48 hours of admission:
rd

3 generation cephalosporin, e.g.:

Ceftriaxone, IV, 1 g daily.
AND

Gentamicin, IV, 6 mg/kg daily.
If IV line, skin infection is suspected as the cause::
ADD:

Vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20
mg/kg/dose 12 hourly. (See Appendix II for guidance on prescribing and
monitoring).
If fever develops after 48 hours of admission:
(Choice of antibiotic will depend on local susceptibility patterns).

Carbapenem with activity against Pseudomonas, e.g.:

Meropenem, IV, 1 g 8 hourly or Imipenem, IV, 500 mg 6 hourly.
Note: Ertapenem is not recommended because it is not effective for
Pseudomonas species, which are important pathogens in this setting.
OR

Piperacillin/tazobactam, IV, 4.5 g 8 hourly
OR

Cefepime, IV, 1 g 12 hourly.
If no response after 5–7 days: (In discussion with a Clinical Haematologist or
Infectious Disease specialist).
ADD

Amphotericin B, IV, 1 mg/kg daily in dextrose 5 % over 4 hours.
o Ensure adequate hydration to minimise nephrotoxicity. (See
Appendix II for preventing, monitoring and management of toxicity).
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BLOOD AND BLOOD FORMING ORGANS
Duration of therapy:
9
» If neutrophil count increases to > 0.5  10 /L, continue for 2 days after
fever has settled.
9
» If neutrophil count remains  0.5  10 /L, continue for 7 days after fever
has settled.
REFERRAL/CONSULTATION
All cases – consult with haematologist/oncologist.
2.9 MYELODYSPLASTIC SYNDROMES
D46
DESCRIPTION
A group of disorders characterised by refractory cytopaenias due to bone
marrow failure. Tthere is a risk of disease progression to acute leukaemia.
Investigations
» Evidence of cytopenia, with normal B12 and folate levels, and often
substantial morphological dysplasia on the blood smear.
» Bone marrow examination confirms dysplasia of the blood elements and
the presence of cytogenetic abnormalities.
TREATMENT
Transfusion should ideally be with leucodepleted red cells to delay
immunisation, as these patients require frequent transfusions.
Bone marrow transplantation can be curative in selected patients.
If neutropenic and febrile, see section 2.8: Febrile neutropenia.
REFERRAL
All patients for further investigation and management.
2.10 BLEEDING DISORDERS
GENERAL PRINCIPLES
A bleeding tendency may result from:
» a coagulation defect (congenital/acquired),
» a vessel wall defect, or
» a platelet defect (quantitative/qualitative).
A careful and detailed history, thorough examination and review of relevant
laboratory investigations will allow differentiation between these three
categories, as the management of each of these groups differs significantly.
Screening tests include: Full Blood Count, prothrombin time (PT) and
activated partial thromboplastin time (aPTT) (if prolonged, mixing studies are
required).
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CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
Patients with a chronic bleeding tendency should be advised to wear a
medic alert bracelet which clearly mentions the type of disorder he/she
suffers from, e.g. severe Haemophilia A, Factor VIII <1%, no inhibitors.
2.10.1 HAEMOPHILIA A AND B, VON WILLEBRAND’S
DISEASE
D66/7/8
DESCRIPTION
Haemophilia A, haemophilia B and von Willebrand's disease are chronic
bleeding disorders caused, respectively, by a lack of clotting factor VIII,
clotting factor IX and von Willebrand factor (VWF, a carrier protein for factor
VIII). Presentation depends on severity of the condition (see classification
below).
Complications include haemarthrosis with later chronic arthropathy,
intracranial haemorrhage, soft tissue and muscle haematomas. Pain/tingling
in a joint suggests bleeding into the joint in a known haemophiliac.
Early consultation with a haematologist or a clinician with expertise in the
handling of such patients is advisable. Clinicians should make contact with
their local haemophilia centre which may be identified at:
http://www.haemophilia.org.za/centres.html
All patients diagnosed with haemophilia should at least annually attend a
specialised Haemophilia Treatment Centre with a dedicated multidisciplinary health care team.
Subclassification (factor VIII and IX deficiency):
CLASS
CLOTTING
FACTOR
Mild
Moderate
Severe
% OF NORMAL
SIGNS
VIII or IX
VIII or IX
>5–<40%
1–5%
VIII or IX
< 1%
Occasional bleeds
Less frequent
bleeding
associated with
trauma, surgery or
dental work
Traumatic or
spontaneous
bleeds
Investigations
Prolonged partial thromboplastin time (PTT).
Factor VIII or factor IX concentration and inhibitor screen.
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BLOOD AND BLOOD FORMING ORGANS
TREATMENT GUIDELINES
Treatment approaches are divided into two main categories: prophylaxis and
on demand.
Prophylaxis
Secondary prophylaxis is sometimes needed in patients presenting with a
target joint in consultation with a Haemophilia Treatment Centre.
The aim is to reduce the number of bleeds and prevent or delay
development of joint arthropathy.
Treatment on Demand
Episodic treatment for bleeding episodes is referred to as on-demand
therapy (i.e. the use of factor replacement therapy after bleeding occurs).
GENERAL MEASURES
»
»
»
»
»
Patient and family education.
Enroll on the Haemophilia registry.
Alert bracelet.
Dental care (discuss management of tooth extraction with local
haemophilia centre).
Avoid contact sport.
Acute bleeds into joints
Patients with severe haemophilia should be trained to self-administer their
clotting factor concentrate.
Adjunctive management
» Protection (splint but no circumferential casting).
» Rest the affected limb until pain free and no weight bearing.
» Ice packs may be applied immediately (apply ice, 5 minutes on and 10
minutes off).
» Elevation of the affected limb.
MEDICINE TREATMENT
For pain: Refer to chapter 12: Anaesthesiology, pain and intensive care.
Exercise great caution when taking blood specimens.
Taking blood from femoral veins is absolutely contra-indicated.
Do not use central lines for transfusions. Do not do joint aspirations
Avoid IM injections.
Avoid aspirin and NSAIDS.
HAEMOPHILIA WITH NO INHIBITORS
The dose of the factor VIII and IX is individualised as it is dependent on body
mass, severity of the condition, and the nature and site of the bleeding.
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Factor VIII deficiency (with no inhibitor present)
Minor bleeds:
Bleeds into the muscle or soft tissue, mouth or gums, epistaxis, painless
haematuria and early joint bleeds.
Treatment:

Factor VIII, intravenous, 25 IU/kg IV, immediately as a single dose.
o If there is evidence of ongoing bleeding after 12 hours, consult with
local haemophilia treatment centre.
Major bleeds:
Advanced muscle or joint bleeds, bleeds resulting from severe injury, or
bleeds that affect the central nervous system; gastrointestinal system; neck
or throat; hip or iliopsoas; or forearm compartment.
Treatment:

Factor VIII, intravenous, 50 IU/kg, immediately as a single dose.
o All of these patients need hospitalization.
o Discuss all patients promptly with local haemophilia treatment
centre.
vii
LoE:III
Factor IX deficiency (with no inhibitor present)
Minor bleeds:
Bleeds into the muscle or soft tissue, mouth or gums, epistaxis, painless
haematuria and early joint bleeds.
Treatment:

Factor IX, intravenous, 40 IU/kg immediately as a single dose.
o If there is evidence of ongoing bleeding after 12 hours, consult with
local haemophilia treatment centre.
Major bleeds:
Major muscle or joint bleeds, bleeds resulting from severe injury, or bleeds
that affect the central nervous system; gastrointestinal system; neck or
throat; hip or iliopsoas; or forearm compartment.
Treatment:

Factor IX, intravenous, 60 IU/kg immediately as a single dose.
o All of these patients need hospitalisation.
Discuss all patients promptly with local haemophilia treatment centre to plan
ongoing treatment and factor replacement.
viii
LoE:III
Mucous membrane bleeds in haemophilia A and B:

Tranexamic acid, oral, 1 g, 6 hourly.
Ideally elective surgery should be perfomed at a tertiary centre with a
consultation with a haematologist.
In emergencies, treat as major bleed and consult the local Haemophilia
Treatment Centre as soon as feasible.
2015
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BLOOD AND BLOOD FORMING ORGANS
If serious bleeding with known haemophilia, and no factor VIII available:

FFP, IV, 15 mL/kg.
OR
Lyophilised plasma, IV, 15 mL/kg.
ix
LoE:II
HAEMOPHILIA WITH INHIBITORS
Refer for assessment and planning with a haematologist.
VON WILLEBRAND’S DISEASE
Mild bleeding
E.g. epistaxis and menorrhagia.
Antifibrinolytics, e.g.:

Tranexamic acid, oral, 1 g 6 hourly.
Recurrent menorrhagia can also be treated effectively with oral contraceptives.
More severe mucous membrane bleeding
Consult a local haemophilia treatment centre.
During surgery or after major trauma, patients should receive:

Von Willebrand factor VIII concentrate, IV, 30 units/kg/dose given every
12 hours.
o Continue for 48–72 hours to ensure optimal haemostasis.
o For major surgical procedures, use for 7–10 days.
LoE:III
REFERRAL
»
»
»
All cases with suspected haemophilia (prolonged PTT and normal INR)
to a haemophilia treatment centre, for assessment, genetic counselling
and planning of management.
Patients with proven antibodies (inhibitors) against factor VIII or IX.
For further replacement, complex situations and complications in
consultation with a haematologist.
2.11 IMMUNE THROMBOCYTOPENIA (ITP)
D69.3
DESCRIPTION
A common bleeding disorder due to immune-mediated destruction of
platelets. Clinically apparent associated conditions, drugs (e.g. penicillins,
cephalosporins, quinine, rifampicin and heparin), or other agents that may
cause thrombocytopenia are NOT present. Patients with suspected ITP
should be tested for SLE and for HIV infection.
Investigations
» Thrombocytopenia with normal white cell count and red cell indices
(however, anaemia may be present due to blood loss).
2015
2.14
CHAPTER 2
»
»
»
BLOOD AND BLOOD FORMING ORGANS
Peripheral blood smear to exclude RBC fragments. Smear may show
large platelets.
Do INR and aPTT, both of which should be normal in ITP.
If there is a poor response to treatment do a bone marrow aspirate and
biopsy.
GENERAL MEASURES
Avoid:
» medication that affects platelet function, e.g. NSAIDs and aspirin,
» platelet transfusions, unless there are life-threatening bleeds,
» dental procedures in acute phase, and
» IM injections.
Reassure the patient that resolution usually occurs in acute ITP.
Medic alert bracelet.
Platelet transfusions may be given if surgery is required or in life-threatening
bleeding.
Goal of treatment: to reduce the risk of bleeding, not to normalize the platelet
count.
Avoid unnecessary treatment of asymptomatic patients with mild to
9
moderate thrombocytopenia (platelet count >30 x 10 /L).
MEDICINE TREATMENT
Acute ITP

Prednisone, oral, 1 mg/kg daily, until platelet count has normalised.
o Taper slowly and monitor platelet count. (Refer to
LoE:III
page xxvii for an example of a dose reduction
regimen).
o Although prednisone is also indicated for HIV-associated immune
thrombocytopenia it is important that all these patients should be
fast-tracked for ART.
Second line therapy
Patients with persistent thrombocytopenia not responding to treatment with
glucocorticoids.
Treatment with specialist supervision
There are other multiple treatments available but are dependent on
specialist opinion.
REFERRAL
»
»
All cases not responding to steroids and, in the case of HIV-infected
patients, not responding to ART – discuss with haematologist.
Refer for second line treatment.
Acute active life-threatening bleeding and surgery

Platelet transfusions.
Platelet transfusions are only indicated in acute active bleeding uncontrolled
2015
2.15
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
by other means or before procedures. In an adult, 1 unit of platelets,
preferably single donor, leucocyte depleted platelets, is usually sufficient to
control the bleeding initially. Platelet transfusions have limited benefit in this
condition as platelets are rapidly destroyed by the immune system.

Methylprednisolone acetate 1 g, IV, daily for 3 days.
x
If the bleeding cannot be controlled, consult with a specialist.
LoE:III
2.12 THROMBOTIC THROMBOCYTOPENIC PURPURAHAEMOLYTIC URAEMIC SYNDROME (TTP-HUS)
M31.1/D59.3
DESCRIPTION
Acute syndromes with abnormalities in multiple organ systems with evidence of
micro-angiopathic haemolytic anaemia and thrombocytopenia.
This condition presents with varying combinations of the following (only some of
which may be present):
» Microangiopathic haemolytic anaemia thrombocytopenia, often with
purpura but not usually severe bleeding,
» acute renal insufficiency,
» neurologic abnormalities, and
» fever.
Microangiopathic haemolytic anaemia is defined as nonimmune haemolysis
with prominent RBC fragmentation (schistocytes) observed on the peripheral
blood smear along with thrombocytopaenia.
TTP-HUS is associated with HIV infection and all patients should be tested
for HIV.
TTP-HUS should be distinguished from disseminated intravascular
coagulation (DIC) and severe pre-eclampsia where the coagulation profile
(PT/PTT) is deranged.
TREATMENT

In HIV-associated thrombotic thrombocytopenia, start combination
antiretroviral therapy urgently.

FFP, IV infusion, 30 mL/kg/day in 3–4 divided doses.
OR
Lyophilised plasma, IV infusion, 30 mL/kg/day in 3–4 divided doses.
xi
LoE:II
The use of platelet transfusions should be discussed with a
specialist.
2015
2.16
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
REFERRAL
All patients – discuss with a haematologist.
2.13 ACQUIRED COAGULATION DEFECTS
2.13.1 DISSEMINATED INTRAVASCULAR COAGULATION
(DIC)
D65
DIC is a complication of an underlying condition and is characterized by
widespread activation of clotting cascade leading to consumption of clotting
factors and platelets with generalized bleeding. No single diagnostic test, but
the combination of a prolonged INR and PTT, thrombocytopenia, decreased
fibrinogen and increased D-dimer is highly suggestive of the diagnosis.
MANAGEMENT
Identify and treat the underlying cause.
If the patient is bleeding, replace haemostatic factors with cryoprecipitate or
FFP/lyophilised plasma.
9
If the patient is not actively bleeding and platelet count > 20 x 10 /L, then
platelet transfusion is not necessary.
Replacement therapy for thrombocytopenia should consist of 1 apheresis
single donor unit or 1 pooled random donor unit. In chronic DIC, or in the
absence of bleeding, platelet transfusions should not be given merely to
correct the thrombocytopenia.
For hypofibrinogenaemia:

Cryoprecipitate, IV, 1 unit/10 kg.
For depletion of other coagulation factors:

FFP, IV, 15 mL/kg as initial dose.
o Volume: ±280 mL/unit.
OR
Lyophilised plasma, IV, 15 mL/kg as initial dose.
o Volume: ±200 mL/unit.
xii
LoE:II
Repeat replacement therapy 8 hourly or less frequently, with adjustment
according to the clinical picture and laboratory parameters.
Monitor response with frequent estimation of the platelet count and
coagulation screening tests.
2015
2.17
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
2.14 VENOUS THROMBO-EMBOLISM
I82
DESCRIPTION
Venous thromboembolism (VTE) should be seen as a spectrum from calf
deep venous thrombosis (DVT) to pulmonary thrombo-embolism. All patients
should be seen as potentially high risk.
Differential diagnosis includes:
» cellulitis
» ruptured popliteal (Baker’s) cyst
» superficial thrombophlebitis
» calf muscle pull or tear
» lymphoedema
» internal derangement of the knee
chronic venous insufficiency
Diagnosis is primarily clinical and confirmed with imaging studies, e.g.
Duplex Doppler.
GENERAL MEASURES
Acute management
Thrombolytic therapy may be indicated in patients with confirmed early
pulmonary embolism where haemodynamic stability cannot be achieved.
Discuss with a specialist.
MEDICINE TREATMENT
Acute treatment
Unfractionated or low molecular weight heparin started simulatenously with
warfarin. After 5 days, heparin may be stopped if a therapeutic INR level has
been reached and maintained for at least 24 hours.
Note: Heparin and warfarin therapy should overlap for at least 5 days.
For proximal venous thrombosis and/or pulmonary embolism:

Unfractionated heparin, SC, 333 units/kg as an initial dose.
o Follow 12 hours later by 250 units/kg/dose 12 hourly.
Units of unfractionated heparin
Volume of heparin in mL
(25 000 units/mL)
Weight (kg)
Loading
12 hourly
Loading
12 hourly
dose
dose (units)
dose
dose
(units)
(mL)
(mL)
35 kg
11 000 units
8 750 units
0.44 mL
0.35 mL
40 kg
13 000 units 10 000 units
0.52 mL
0.4 mL
45 kg
15 000 units 11 250 units
0.6 mL
0.45 mL
50 kg
17 000 units 12 500 units
0.67 mL
0.5 mL
55 kg
18 000 units 13 750 units
0.73 mL
0.55 mL
60 kg
20 000 units 15 000 units
0.8 mL
0.6 mL
65 kg
22 000 units 16 250 units
0.87 mL
0.65 mL
70 kg
23 000 units 17 500 units
0.93 mL
0.7 mL
75 kg
25 000 units 18 750 units
1 mL
0.75 mL
80 kg
27 000 units 20 000 units
1.07 mL
0.8 mL
2015
2.18
CHAPTER 2
85 kg
90 kg
BLOOD AND BLOOD FORMING ORGANS
28 000 units
30 000 units
21 250 units
22 500 units
1.13 mL
1.2 mL
0.85 mL
0.9 mL
Evidence indicates that PTT monitoring is not necessary with weight based
dosing of unfractionated heparin. However, in patients with morbid obesity
and renal failure (eGFR < 30 mL/minute) unfractionated heparin should be
used with PTT monitoring to maintain the PTT at 1.5 to 2.5 times the control.
PTT should be taken 4 hours after SC dose.
OR

Low molecular weight heparin, e.g.:

Enoxaparin, SC, 1 mg/kg 12 hourly.
LoE:III
In morbid obesity dosing of LMWH should be individualised, in discussion
xiii
with a specialist.
LoE:III
In renal failure (eGFR < 30 mL/minute), the recommended dose of LMWH is
xiv
1 mg/kg/day.
LoE:III
Follow with:

Warfarin, oral, 5 mg daily.
o INR should be done after 48 hours, then every 1 to 2 days until
within the therapeutic range of 2 to 3 (refer to Initiation dosing
tables in the Appendix II).
o Adjust dose to keep INR within therapeutic range (refer to
Maintenance dosing tables in the Appendix II).
o Continue warfarin for 3 months with regular INR monitoring if there
was a precipitating cause that has resolved.
o In patients with a first unprovoked DVT, discuss duration of therapy
with a specialist.
o Contraindications for warfarin: first trimester and the last month of
pregnancy. In these instances, replace with heparin.
o For all major elective surgery and other elective procedures with a
significant bleeding risk, such as neuraxial anaesthesia and lumbar
punctures, the INR should be <1.5.
Prophylaxis

Prophylaxis is indicated for most medical and surgical patients.
Unfractionated heparin, SC, 5 000 units 12 hourly.
OR

Low molecular weight heparin, e.g.:

Enoxaparin, SC, 40 mg daily.
2015
LoE:III
2.19
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
In morbid obesity dosing of LMWH should be individualised, in discussion
xv
LoE:III
with a specialist.
In renal failure (eGFR < 30 mL/minute), the recommended dose of LMWH is
xvi
LoE:III
1 mg/kg/day.
Although the risk of bleeding is small, in the following patients prophylaxis
should only be used under exceptional circumstances:
» active bleeding,
» intraocular, intracranial or spinal surgery,
» lumbar puncture or spinal/epidural anaesthesia within 12 hours after
prophylactic dose or 24 hr of full therapeutic dose,
(Timing of anticoagulants for patients receiving anaesthesia: See
section 12.8: Spinal (intrathecal) anaesthesia).
» renal insufficiency,
» coagulopathy, or
» uncontrolled hypertension.
Heparin induced thrombocytopenia
A severe immune-mediated drug reaction occurring in 1–5% of patients
receiving heparin (more common with unfractionated heparin, but may also
occur with low molecular weight heparin) therapy. It presents with
thrombocytopenia and thrombosis. Diagnosis needs a high index of
suspicion and should be considered if a patient has a 50% drop in platelet
count within 5–10 days after initiating heparin therapy. Confirmation is done
by positive antibody testing.
Stop heparin and discuss all patients with a specialist.
REFERRAL/CONSULTATION
Heparin-induced thrombocytopenia.
References:
i
Ferrous sulphate BPC: SAMF, 2014.
Ferrous sulphate BPC (duration of therapy): Alleyne M, Horne MK, Miller JL. Individualized treatment for irondeficiency anemia in adults. Am J Med. 2008 Nov;121(11):943-8. http://www.ncbi.nlm.nih.gov/pubmed/18954837
ii
Ferrous sulphate BPC: SAMF, 2014.
iii
Low molecular weight iron dextran: Atalay H, Solak Y, Acar K, Govec N, Turk S. Safety profiles of total dose
infusion of low-molecular-weight iron dextran and high-dose iron sucrose in renal patients. Hemodial Int. 2011
Jul;15(3):374-8. http://www.ncbi.nlm.nih.gov/pubmed/21564503
Low molecular weight iron dextran: Solak Y, Atalay H, Guney I, Turkmen K, Kaya E, Turk S. Comparison of
adverse-event profiles of intravenous low-molecular-weight iron dextran and iron sucrose in peritoneal dialysis
patients. Ren Fail. 2011;33(3):307-11. http://www.ncbi.nlm.nih.gov/pubmed/21401355
iv
Prednisone: Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of
Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune
thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. http://www.ncbi.nlm.nih.gov/pubmed/21325604
v
Immunosuppresive therapy (e.g. Azathioprine): Hitzig WH, Massimo L. Treatment of autoimmune hemolytic
anemia in children with azathioprine (imuran). Blood. 1966 Dec;28(6):840-50.
http://www.ncbi.nlm.nih.gov/pubmed/5959475
Immunosuppresive therapy (e.g. Azathioprine): Worlledge SM, Brain MC, Cooper AC, Hobbs JR, Dacie JV.
Immmunosuppressive drugs in the treatment of autoimmune haemolytic anaemia. Proc R Soc Med. 1968 Dec
2015
2.20
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
12;61(12):1312-5. http://www.ncbi.nlm.nih.gov/pubmed/4177973
vi
Enoxaparin: Wein L, Wein S, Haas SJ, Shaw J, Krum H. Pharmacological venous thromboembolism prophylaxis
in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Jul
23;167(14):1476-86. http://www.ncbi.nlm.nih.gov/pubmed/17646601
vii
Factor VIII: World Federation of Haemophilia. 2012. Guidelines for Management of Haemophilia.
http://www1.wfh.org/publication/files/pdf-1472.pdf
Factor VIII: Mahlangu JN, Gilham A. Guideline for the Treatment of Haemophilia in South Africa. S Afr Med J
2008; 98: 125-140. http://www.samj.org.za/index.php/samj/article/view/336/723
viii
Factor IX: World Federation of Haemophilia. 2012. Guidelines for Management of Haemophilia.
http://www1.wfh.org/publication/files/pdf-1472.pdf
Factor IX: Mahlangu JN, Gilham A. Guideline for the Treatment of Haemophilia in South Africa. S Afr Med J
2008; 98: 125-140. http://www.samj.org.za/index.php/samj/article/view/336/723
ix
Lyophilised plasma: Bindi ML, Miccoli M, Marietta M, Meacci L, Esposito M, Bisà M, Mozzo R, Mazzoni A, Baggiani
A, Scatena F, Filipponi F, Biancofiore G. Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver
transplant surgery: a prospective randomized control study. Vox Sang. 2013 Aug;105(2):137-43.
http://www.ncbi.nlm.nih.gov/pubmed/23448618
Lyophilised plasma: Lerner RG, Nelson J, Sorcia E, Grima K, Kancherla RR, Zarou-Naimo CM, Pehta JC.
Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang.
2000;79(3):161-7. http://www.ncbi.nlm.nih.gov/pubmed/11111235
Lyophilised plasma: Williamson LM, Llewelyn CA, Fisher NC, Allain JP, Bellamy MC, Baglin TP, Freeman J, Klinck
JR, Ala FA, Smith N, Neuberger J, Wreghitt TG. A randomized trial of solvent/detergent-treated and standard freshfrozen plasma in the coagulopathy of liver disease and liver transplantation. Transfusion. 1999 Nov-Dec;39(1112):1227-34. http://www.ncbi.nlm.nih.gov/pubmed/10604250
Lyophilised plasma: Huisman EL, de Silva SU, de Peuter MA. Economic evaluation of pooled solvent/detergent
treated plasma versus single donor fresh-frozen plasma in patients receiving plasma transfusions in the United States.
Transfus Apher Sci. 2014 Aug;51(1):17-24. http://www.ncbi.nlm.nih.gov/pubmed/25151097
x
Methylprednisilone, IV: Alpdogan O, Budak-Alpdogan T, Ratip S, Firatli-Tuglular T, Tanriverdi S, Karti S, Bayik
M, Akoglu T. Efficacy of high-dose methylprednisolone as a first-line therapy in adult patients with idiopathic
thrombocytopenic purpura. Br J Haematol. 1998 Dec;103(4):1061-3. http://www.ncbi.nlm.nih.gov/pubmed/9886319
xi
Lyophilised plasma: Bindi ML, Miccoli M, Marietta M, Meacci L, Esposito M, Bisà M, Mozzo R, Mazzoni A, Baggiani
A, Scatena F, Filipponi F, Biancofiore G. Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver
transplant surgery: a prospective randomized control study. Vox Sang. 2013 Aug;105(2):137-43.
http://www.ncbi.nlm.nih.gov/pubmed/23448618
Lyophilised plasma: Lerner RG, Nelson J, Sorcia E, Grima K, Kancherla RR, Zarou-Naimo CM, Pehta JC.
Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang.
2000;79(3):161-7. http://www.ncbi.nlm.nih.gov/pubmed/11111235
Lyophilised plasma: Williamson LM, Llewelyn CA, Fisher NC, Allain JP, Bellamy MC, Baglin TP, Freeman J, Klinck
JR, Ala FA, Smith N, Neuberger J, Wreghitt TG. A randomized trial of solvent/detergent-treated and standard freshfrozen plasma in the coagulopathy of liver disease and liver transplantation. Transfusion. 1999 Nov-Dec;39(1112):1227-34. http://www.ncbi.nlm.nih.gov/pubmed/10604250
Lyophilised plasma: Huisman EL, de Silva SU, de Peuter MA. Economic evaluation of pooled solvent/detergent
treated plasma versus single donor fresh-frozen plasma in patients receiving plasma transfusions in the United States.
Transfus Apher Sci. 2014 Aug;51(1):17-24. http://www.ncbi.nlm.nih.gov/pubmed/25151097
xii
Lyophilised plasma: Bindi ML, Miccoli M, Marietta M, Meacci L, Esposito M, Bisà M, Mozzo R, Mazzoni A, Baggiani
A, Scatena F, Filipponi F, Biancofiore G. Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver
transplant surgery: a prospective randomized control study. Vox Sang. 2013 Aug;105(2):137-43.
http://www.ncbi.nlm.nih.gov/pubmed/23448618
Lyophilised plasma: Lerner RG, Nelson J, Sorcia E, Grima K, Kancherla RR, Zarou-Naimo CM, Pehta JC.
Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang.
2000;79(3):161-7. http://www.ncbi.nlm.nih.gov/pubmed/11111235
Lyophilised plasma: Williamson LM, Llewelyn CA, Fisher NC, Allain JP, Bellamy MC, Baglin TP, Freeman J, Klinck
JR, Ala FA, Smith N, Neuberger J, Wreghitt TG. A randomized trial of solvent/detergent-treated and standard freshfrozen plasma in the coagulopathy of liver disease and liver transplantation. Transfusion. 1999 Nov-Dec;39(1112):1227-34. http://www.ncbi.nlm.nih.gov/pubmed/10604250
Lyophilised plasma: Huisman EL, de Silva SU, de Peuter MA. Economic evaluation of pooled solvent/detergent
treated plasma versus single donor fresh-frozen plasma in patients receiving plasma transfusions in the United States.
Transfus Apher Sci. 2014 Aug;51(1):17-24. http://www.ncbi.nlm.nih.gov/pubmed/25151097
xiii
Low molecular weight heparin (morbid obesity): Lalama JT, Feeney ME, Vandiver JW, Beavers KD, Walter LN,
McClintic JR. Assessing an enoxaparin dosing protocol in morbidly obese patients. J Thromb
Thrombolysis. 2015 May;39(4):516-21. doi: 10.1007/s11239-014-1117-y.
http://www.ncbi.nlm.nih.gov/pubmed/25087072
Low molecular weight heparin (morbid obesity): Spinler SA, Inverso SM, Cohen M, Goodman SG, Stringer KA,
Antman EM; ESSENCE and TIMI 11B Investigators. Safety and efficacy of unfractionated heparin versus
enoxaparin in patients who are obese and patients with severe renal impairment:
analysis from the ESSENCE and TIMI 11B studies. Am Heart J. 2003 Jul;146(1):33-41.
http://www.ncbi.nlm.nih.gov/pubmed/12851605
Low molecular weight heparin (morbid obesity): Thompson-Moore NR, Wanat MA, Putney DR, Liebl PH,
Chandler WL, Muntz JE. Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized
2015
2.21
CHAPTER 2
BLOOD AND BLOOD FORMING ORGANS
Patients With Morbid Obesity. Clin Appl Thromb Hemost. 2015 Sep;21(6):513-20.
http://www.ncbi.nlm.nih.gov/pubmed/25601898
Low molecular weight heparin (morbid obesity): Freeman A, Horner T, Pendleton RC, Rondina MT. Prospective
comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill
patients with extreme obesity. Am J Hematol. 2012 Jul;87(7):740-3. http://www.ncbi.nlm.nih.gov/pubmed/22565589
xiv
Low molecular weight heparin (renal impairment): SAMF, 2014.
xv
Low molecular weight heparin (morbid obesity): Lalama JT, Feeney ME, Vandiver JW, Beavers KD, Walter LN,
McClintic JR. Assessing an enoxaparin dosing protocol in morbidly obese patients. J Thromb
Thrombolysis. 2015 May;39(4):516-21. doi: 10.1007/s11239-014-1117-y.
http://www.ncbi.nlm.nih.gov/pubmed/25087072
Low molecular weight heparin (morbid obesity): Spinler SA, Inverso SM, Cohen M, Goodman SG, Stringer KA,
Antman EM; ESSENCE and TIMI 11B Investigators. Safety and efficacy of unfractionated heparin versus
enoxaparin in patients who are obese and patients with severe renal impairment:
analysis from the ESSENCE and TIMI 11B studies. Am Heart J. 2003 Jul;146(1):33-41.
http://www.ncbi.nlm.nih.gov/pubmed/12851605
Low molecular weight heparin (morbid obesity): Thompson-Moore NR, Wanat MA, Putney DR, Liebl PH,
Chandler WL, Muntz JE. Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized
Patients With Morbid Obesity. Clin Appl Thromb Hemost. 2015 Sep;21(6):513-20.
http://www.ncbi.nlm.nih.gov/pubmed/25601898
Low molecular weight heparin (morbid obesity): Freeman A, Horner T, Pendleton RC, Rondina MT. Prospective
comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill
patients with extreme obesity. Am J Hematol. 2012 Jul;87(7):740-3. http://www.ncbi.nlm.nih.gov/pubmed/22565589
xvi
Low molecular weight heparin (renal impairment): SAMF, 2014.
2015
2.22
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.1 ISCHAEMIC HEART DISEASE AND ATHEROSCLEROSIS,
PREVENTION
I20-I25
Major risk factors for ischaemic cardio- and cerebrovascular disease:
» Diabetes mellitus.
» Hypertension.
» Central obesity (waist circumference): men ≥ 102 cm, women ≥ 88 cm.
» Smoking.
» Dyslipidaemia:
- Total cholesterol > 5.0 mmol/L, or
- LDL > 3 mmol/L, or
- HDL < 1 mmol/L in men and < 1.2 mmol/L in women.
» Family history of premature cardiovascular disease in first degree male
relatives < 55 years and in first degree female relatives < 65 years.
» Age: men > 55 years, women > 65 years.
i
» Psychological stress.
LoE:II
GENERAL MEASURES
Lifestyle modification, especially smoking cessation, is essential and
often has greater benefit on prognosis than vascular interventions and
medications.
All persons should be encouraged to make the following lifestyle changes as
appropriate:
» Smoking cessation.
2
» Weight reduction in overweight patients, i.e. BMI > 25 kg/m .
2
» Maintain ideal weight, i.e. BMI < 25 kg/m .
» Reduce alcohol intake to no more than 2 standard drinks/day
» Follow a prudent eating plan i.e. low saturated fat, high fibre and
unrefined carbohydrates, with adequate fresh fruit and vegetables.
» Moderate aerobic exercise, e.g. 40 minutes brisk walking at least 3 times
a week.
2015
3.1
CHAPTER 3
CARDIOVASCULAR SYSTEM
Calculation of risk of developing cardiovascular disease over 10 years
(in the absence of cardiovascular disease)
To derive the absolute risk as the percentage of patients who will have a
myocardial infarction over 10 years, add the points for each risk category
(Section A). The risk associated with the total points is then derived from
Section B.
SECTION A
Age
(years)
MEN
WOMEN
0
2
5
6
8
10
11
12
14
15
0
2
4
5
7
8
9
10
11
12
Total cholesterol
(mmol/L)
< 4.1
4.1–5.1
5–6.2
6.2–7.2
> 7.2
MEN
WOMEN
0
1
2
3
4
0
1
3
4
5
HDL cholesterol
(mmol/L)
> 1.6
1.3–1.5
1.2–1.3
0.9–1.1
< 0.9
MEN
WOMEN
–2
1
0
1
2
–2
–1
0
1
2
MEN
4
3
WOMEN
3
4
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–69
70–74
75–79
Smoker
Diabetic*
*Type 2 diabetics >40 years, qualify for statin therapy irrespective of risk score.
MEN
Systolic
(mmHg)
< 120
120–129
130–139
140–149
150–159
≥ 160
2015
BP
Untreated
Treated
–2
0
1
2
2
3
0
2
3
4
4
5
WOMEN
Untreated
Treated
–3
0
1
2
4
5
–1
2
3
5
6
7
3.2
CHAPTER 3
CARDIOVASCULAR SYSTEM
SECTION B
Total points
10-year risk %
<1
1.1
1.4
1.6
1.9
2.3
2.8
3.3
3.9
4.7
5.6
6.7
7.9
9.4
11.2
13.2
15.6
18.4
21.6
25.3
29.4
>30
MEN
≤ –3
–2
–1
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
≥18
10-year risk %
<1
1.0
1.2
1.5
1.7
2.0
2.4
2.8
3.3
3.9
4.5
5.3
6.3
7.3
8.6
10.0
11.7
13.7
15.9
18.5
21.5
24.8
28.5
>30
WOMEN
≤–2
–1
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21+
MEDICINE TREATMENT
Indication for lipid lowering medication:
Secondary prevention (irrespective of baseline cholesterol levels):
» Established atherosclerotic disease, irrespective of cholesterol or
triglyceride plasma concentrations:
 ischaemic heart disease,
 peripheral vascular disease, or
 atherothrombotic stroke.
» Type 2 diabetics > 40 years of age, or diabetes for > 10 years, or
cardiovascular disease, or chronic kidney disease (eGFR < 60
ii
mL/minute)
LoE:I
OR
Primary prevention:
» A risk of MI of greater than 20% in 10 years (see table above).


HMGCoA reductase inhibitors (statins) that lower LDL-cholesterol by at
least 25%, e.g.:
iii
LoE:I
Simvastatin, oral, 10 mg at night.
Note: Lipid-lowering medicines must always be used in conjunction with
ongoing lifestyle modification.
2015
3.3
CHAPTER 3
CARDIOVASCULAR SYSTEM
REFERRAL
» Random cholesterol > 7.5 mmol/L.
» Fasting (14 hours) triglycerides > 10 mmol/L.
3.2 ACUTE CORONARY SYNDROMES
These conditions should be managed in a high care setting with continuous
ECG and frequent BP monitoring.
3.2.1 ST ELEVATION MYOCARDIAL INFARCTION (STEMI)
I21.0-I21.3
DESCRIPTION
Ischaemic chest pain that is ongoing > 30 minutes and associated with
persistent ST elevation or new or presumed new left bundle branch block
(LBBB). Repeat ECG regularly as clinically indicated.
MEDICINE TREATMENT
If hypoxic:
 Oxygen.
iv
LoE:I
 Clopidogrel, oral, 75 mg daily for one month.
AND
 Aspirin, oral, 150 mg immediately as a single dose (chewed or
dissolved).
o Followed with 150 mg daily (continued indefinitely in absence of
contraindications).
LoE:III
AND
Thrombolytic therapy (see table for time window below):
 Thrombolytic, e.g.:
v
LoE:I
 Streptokinase, IV 1.5 million units diluted in 100 mL
sodium chloride 0.9%, infused over 30–60 minutes. Do
not use heparin if streptokinase is given.
o Hypotension may occur. If it does, reduce the rate of infusion but
strive to complete it in < 60 minutes.
o Streptokinase is antigenic and should not be re-administered in the
st
period of 5 days to 2 years after 1 administration.
o
Severe allergic reactions are uncommon but antibodies which may
render it ineffective may persist for years.
2015
3.4
CHAPTER 3
»
CARDIOVASCULAR SYSTEM
Indications
Contra-indications
For acute myocardial
» Absolute:
infarction with ST elevation
- streptokinase used within the last
or left bundle branch block
year,
- if history of onset is less
- previous allergy,
than 6 hours. (Beyond 6
- CVA within the last 3 months,
hours treat as NSTEMI
- history of recent major trauma,
(see below),
- bleeding within the last month,
- if on-going ischaemic
- aneurysms,
pain.
- brain or spinal surgery or head injury
vi
within the preceding month, or
LoE:I
- active bleeding or known bleeding
disorder.
» Relative:
o refractory hypertension,
o warfarin therapy,
o recent retinal laser treatment,
o subclavian central venous catheter,
o pregnancy,
o TIA in the preceding 6 months,
o traumatic resuscitation.
Adjunctive treatment
For pain:
 Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Pain not responsive to this dose may suggest ongoing unresolved
ischaemia.
 Nitrates, e.g.:
 Isosorbide dinitrate, SL, 5 mg immediately as a single dose.
o May be repeated at 5-minute intervals for 3 or 4 doses.
For ongoing chest pain, control hypertension or pulmonary oedema:
 Glyceryl trinitrate, IV, 5–200 mcg/minute, titrated to response.
o Start with 5 mcg/minute and increase by 5 mcg/minute every 5 minutes
until response or until the rate is 20 mcg/minute.
o No response after 20 mcg/minute, increase by 20 mcg/minute every 5
minutes until a pain response or medicine is no longer tolerated.
o Flush the PVC tube before administering the medicine to patient.
o Monitor BP carefully.
2015
3.5
CHAPTER 3
CARDIOVASCULAR SYSTEM
Dilution of Glyceryl trinitrate:
Volume of diluent
250 mL
500 mL
Solution
Concentration
(mcg/mL)
Dose (mcg/min)
5
10
15
20
30
40
60
80
100
120
160
200
Glyceryl trinitrate
5mg/mL
5 mL (25 mg)
10 mL (50 mg)
20 mL (100 mg)
10 mL (50 mg)
20 mL (100 mg)
40 mL (200 mg)
100 mcg/mL
solution
Concentration of
dilution
100 mcg/mL
200 mcg/mL
400 mcg/mL
100 mcg/mL
200 mcg/mL
400 mcg/mL
200 mcg/mL
solution
400 mcg/mL
solution
Flow rate (microdrops/min = mL/hour)
3
—
—
6
3
—
9
—
—
12
6
3
18
9
—
24
12
6
36
18
9
48
24
12
60
30
15
72
36
18
96
48
24
–
60
30
When clinically stable without signs of heart failure, hypotension,
bradydysrhythmias or asthma:
 Cardio-selective -blocker, e.g.:
 Atenolol, oral, 50 mg daily.


HMGCoA reductase inhibitors (statins) that lower LDL by at least 25%,
e.g.:
vii
LoE:I
Simvastatin oral, 10 mg daily at night.
For LV dysfunction following myocardial infarction, heart failure or ejection
fraction < 40%:
 ACE-inhibitor, e.g.:
 Enalapril, oral 10 mg 12 hourly.
Angioedema is a potentially serious complication of ACE-inhibitor treatment
and if it occurs it is a contraindication to continued therapy or to rechallenge.
2015
3.6
CHAPTER 3
CARDIOVASCULAR SYSTEM
REFERRAL
»
»
»
»
»
»
»
»
Refractory cardiogenic shock.
Refractory pulmonary oedema.
Haemodynamically compromising ventricular dysrhythmia.
Patients with the combination of new right bundle and posterior fascicular
block post MI should be referred for permanent pacemaker consideration
as they are high risk for progression to completer heart blocks.
Myocardial infarction-related mitral regurgitation or ventricular septal
defect (VSD).
Contraindication to thrombolytic therapy (only if within the period for
stenting).
Ongoing ischaemic chest pain.
Failed reperfusion (< 50% reduction in ST elevation at 90 minutes in
leads showing greatest ST elevation, especially in anterior infarct or
inferior infarct with right ventricular involvement).
3.2.2 NON-ST ELEVATION MYOCARDIAL INFARCTION
(NSTEMI) AND UNSTABLE ANGINA (UA)
I21.4/I20.0
DESCRIPTION
Non-ST elevation MI: Chest pain that is increasing in frequency and/or
severity, or occurring at rest. The chest pain is associated with elevated
cardiac biomarkers and ST segment depression or T wave inversion on
ECG. Biomarker elevation in the absence of diagnostic ECG changes should
prompt consideration of alternative diagnoses (e.g. heart failure, pulmonary
embolism, chronic kidney disease, sepsis, myopericarditis.
Unstable angina pectoris: Chest pain that is increasing in frequency and or
severity, or occurring at rest. It also encompasses post-infarct angina. The
chest pain may be associated with ST segment depression or T wave
inversion on ECG. There is no rise in cardiac biomarkers.
MEDICINE TREATMENT
If hypoxic:
 Oxygen.
viii
LoE:I
Clopidogrel, oral, 300 mg.
o Followed by 75 mg daily for 3 months.
AND
 Aspirin, oral, 150 mg immediately as a single dose (chewed or
dissolved).
o Followed with 150 mg daily (continued indefinitely in absence of
contraindications).
LoE:III
AND

2015
3.7
CHAPTER 3
CARDIOVASCULAR SYSTEM
Anticoagulation:
For NSTEMI and UA (also for STEMI not given thrombolytic therapy):
 Parenteral anticoagulation, e.g.:
 Enoxaparin, SC, 1 mg/kg 12 hourly for minimum of 2 days.
OR
 Unfractionated heparin, IV bolus, 5 000 units.
o Follow with 1 000–1 200 units hourly monitored by aPTT.
o Continue infusion for minimum of 2 days.
ix
LoE:I
To relieve spasm and pain and to reduce preload:
 Isosorbide dinitrate SL, 5 mg immediately as a single dose.
o May be repeated at 5-minute intervals for 3 or 4 doses.
For persistent pain and if oral therapy is insufficient:
 Glyceryl trinitrate, IV, 5–200 mcg/minute, titrated to response.
o Start with 5 mcg/minute and increase by 5 mcg/minute every 5
minutes until response or until the rate is 20 mcg/minute.
o If no response after 20 mcg/minute, increase by 20 mcg/minute
every 5 minutes until pain response or medicine no longer
tolerated.
o Flush the PVC tube before administering the medicine to patient.
o Monitor BP carefully.
For dilution of glyceryl trinitrate refer to section 3.2.1: ST elevation
myocardial infarction (STEMI).
For pain:
 Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
o Pain not responsive to this dose may suggest ongoing unresolved
ischaemia.
When clinically stable without signs of heart failure, hypotension,
bradydysrhythmias or asthma:
 Cardio-selective -blocker, e.g.:
 Atenolol, oral, 50 mg daily.


HMGCoA reductase inhibitors (statins) that lower LDL by at least 25%,
e.g.:
x
LoE:I
Simvastatin oral, 10 mg daily at night.
If there is cardiac failure or LV dysfunction:
 ACE-inhibitor, e.g.:
 Enalapril, oral, target dose 10 mg 12 hourly.
2015
xi
LoE:III
3.8
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.2.3 CHRONIC MANAGEMENT OF STEMI / NSTEMI / UA
I21.0-I21.3/ I21.4/I20.0
GENERAL MEASURES
Lifestyle modification. See section 3.1: Ischaemic heart disease and
atherosclerosis, prevention.
MEDICINE TREATMENT
Continue oral therapy as above.
If heart failure develops, replace atenolol with:
 Carvedilol, oral.
See section 3.4: Congestive cardiac failure.
REFERRAL
»
»
Patients with a diagnosis of NTSEMI should be risk stratified at
presentation to estimate their likelihood of developing a major adverse
cardiac event (acute MI, heart failure, death or readmission for UA) over
the subsequent 4-6 weeks. High risk patients should be referred to a
cardiology service for angiography and revascularization therapy,
provided that personnel and facilities are available that will allow
diagnostic coronary angiography and revascularization by means of
percutaneous intervention or coronary bypass surgery within 7 days of
the index event. Two widely used and well validated risk stratification
scores are TIMI (http://www.mdcalc.com/timi-risk-score-for-uanstemi/)
and Grace Risk Scores (http://www.mdcalc.com/grace-acs-risk-andmortality-calculator).
Other important indications for referral include ongoing chest pain, postinfarct angina, sustained dysrhythmias or refractory heart failure.
3.2.4 ANGINA PECTORIS, STABLE
I20.0-I20.9
DESCRIPTION
Characteristic chest pain due to myocardial ischaemia usually occurring on
exercise and relieved by rest. Discomfort may occasionally be experienced
in a site of referral (shoulder, jaw) but the characteristic provocation by
exercise and relief by rest is a valuable clue.
GENERAL MEASURES
Lifestyle modification. See section 3.1: Ischaemic heart disease and
atherosclerosis, prevention.
MEDICINE TREATMENT
Long-term prophylaxis for thrombosis:
 Aspirin, oral, 150 mg daily.
2015
LoE:III
3.9
CHAPTER 3
CARDIOVASCULAR SYSTEM
AND
Relief of angina:
 Nitrates, short acting e.g.:
 Isosorbide dinitrate, SL, 5 mg.
o May be repeated if required at 5-minute intervals for 3 or 4 doses.
o Instruct patients to keep the tablets in the airtight and lightproof
container in which they are supplied.
o Instruct patients that nitrates are not addictive.
o Instruct patients to use prophylactically, before activities which may
provoke angina.
AND
Step 1
 Atenolol, oral, 50–100 mg daily.
o Titrate to resting heart rate of approximately 60 beats/minute.
If ß-blocker cannot be tolerated or is contraindicated, use long acting calcium
channel blocker.
Step 2
ADD
 Amlodipine, oral, 5 mg daily.
o
Increase to 10 mg daily if required.
Step 3
ADD
 Organic nitrates, e.g.:
 Isosorbide dinitrate, oral, 20–40 mg.
o Taken at 8:00 and 14:00 as this provides a nitrate-free period to
prevent tolerance.
o Modify for night shift workers.


HMGCoA reductase inhibitors, e.g.:
Simvastatin, oral, 10 mg at night.
xii
LoE:I
REFERRAL
»
»
When diagnosis is in doubt, despite exercise stress testing.
Failed medical therapy. A common reason for “failed” therapy is that the
patient has an alternative diagnosis. Therefore this conclusion should be
reached after reasonable effort for non-invasive diagnosis including
exercise stress test.
3.2.5 ATHEROSCLEROTIC PERIPHERAL ARTERIAL
DISEASE
I25.0
DESCRIPTION
History and palpation of pulses confirms diagnosis.
2015
3.10
CHAPTER 3
CARDIOVASCULAR SYSTEM
GENERAL MEASURES
Smoking cessation is essential and is the single most important intervention
to prevent progression.
Exercise within exercise tolerance and other lifestyle modifications.
See section 3.1: Ischaemic heart disease and atherosclerosis, prevention.
MEDICINE TREATMENT
Long-term prophylaxis for thrombosis:
 Aspirin, oral, 150 mg daily.


LoE:III
HMGCoA reductase inhibitors, e.g.:
xiii
LoE:I
Simvastatin, oral, 10 mg daily.
Therapy should be initiated together with appropriate
lifestyle modification. See section 3.1: Ischaemic heart disease and
atherosclerosis, prevention.
REFERRAL
Ongoing vascular insufficiency, which may be surgically reversible.
3.3 CARDIAC DYSRHYTHMIAS
Exclude underlying structural cardiac disease in all patients with cardiac
dysrhythmias.
3.3.1 NARROW QRS COMPLEX (SUPRAVENTRICULAR)
TACHYDYSRHYTHMIAS
I47.1
DESCRIPTION
Sustained (> 30 seconds) or non-sustained narrow QRS (≤ 0.1 seconds)
tachycardias.
REFERRAL
»
»
»
»
2015
Poor rate control.
Frequent or severe symptoms for curative radiofrequency catheter
ablation.
All symptomatic Wolf-Parkinson-White (WPW) syndrome patients (sinus
rhythm ECG shows delta waves) for radiofrequency catheter ablation.
Asymptomatic patients in whom the WPW pattern is detected on ECG
do not need referral.
3.11
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.3.1.1 ATRIAL FIBRILLATION
I48.0-I48.9
Acute onset (< 48 hours)
Assess clinically, e.g. heart failure, mitral stenosis, thyrotoxicosis,
hypertension, age and other medical conditions.
Consider anticoagulation with warfarin (see table below on CHA2DS2-VASc
Score).
Synchronised direct current (DC) cardioversion is occasionally necessary in
haemodynamic instability.
Non-acute/chronic (> 48 hours)
As above, but not immediate DC cardioversion, unless
haemodynamic instability.
there is
MEDICINE TREATMENT
The main aims of therapy for patients with atrial fibrillation should be:
1. Reduction of stroke and systemic embolic risk.
2. Rate control.
3. Relief of symptoms attributed to the atrial fibrillations.
Patients < 65 years of age with no heart diseases or other risk factors may
be managed with aspirin alone.
A simple scoring system allows calculation of risk of stroke in patients with
atrial fibrillation.
CHA2DS2-VASc Score:
Risk Factor
Congestive heart failure/LV dysfunction
Hypertension
Age ≥ 75 years of age
Diabetes mellitus
Stroke/TIA/Thromboembolism
Vascular disease
Age 65–74 years of age
Sex (female gender)
Score
1
1
2
1
2
1
1
1
Source: Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke
and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial
fibrillation. Chest. 2010 Feb;137(2):263-72. http://www.ncbi.nlm.nih.gov/pubmed/19762550
»
»
2015
If patient has a score of one, use either aspirin or warfarin. When score
is ≥ 2, use warfarin or equivalent. The higher the score the greater the
risk of stroke and therefore the more compelling the use of effective
anticoagulation.
Note: This score has been developed on patients with non-valvular
atrial fibrillation and may not be applicable to patients with atrial
fibrillation and rheumatic mitral valve disease. Anticoagulation has not
been tested in this population but most authorities favour
anticoagulation.
3.12
CHAPTER 3
CARDIOVASCULAR SYSTEM
Initial therapy aimed at stroke reduction
Anticoagulate with warfarin:

Warfarin, oral, 5 mg daily.
o INR should be done after 48 hours, then every 1 to 2 days until
within the therapeutic range of 2 to 3 (refer to Initiation dosing
tables in Appendix II).
o Adjust dose to keep INR within therapeutic range (refer to
Maintenance dosing tables in Appendix II).
For therapy aimed at rate control
 Atenolol, oral, 50–100 mg daily.
o Contraindicated in asthmatics, heart failure.
OR
If in CCF:
 Carvedilol, oral.
See section 3.4: Congestive cardiac failure.
AND
If control not adequate add:
 Digoxin, oral, 0.125 mg daily, adjust according to rate response and
trough plasma level
o Digoxin trough plasma levels (before the morning dose) should be
maintained between 0.6-1 nmol/L.
o Patients at high risk of digoxin toxicity are:
 the elderly,
 patients with renal dysfunction,
 hypokalaemia, and
xiv
LoE:II
 patients with lean body mass.
If -blockers are contra-indicated, e.g. asthma or severe peripheral vascular
disease:
 Verapamil, oral, 40–120 mg 8 hourly.
o Titrate against ventricular rate (verapamil is negatively inotropic,
therefore avoid in heart failure due to left ventricular dysfunction).
xv
LoE:III
If not controlled on these agents, refer to specialist for consideration of
alternative therapy, e.g. amiodarone or atrioventricular node ablation and
pacemaker insertion.
DC cardioversion in selected cases, after 4 weeks warfarin anticoagulation.
Long-term therapy
Continue warfarin anticoagulation long-term, unless contra-indicated:
 Warfarin, oral, 5 mg daily.
o Control with INR to therapeutic range:
 INR between 2–3 and patient stable: do 3 monthly monitoring.
2015
3.13
CHAPTER 3

CARDIOVASCULAR SYSTEM
INR < 1.5 or > 3.5: do monthly monitoring.
Caution
Warfarin use requires regular INR monitoring and dose adjustment
according to measured INR.
For rate control:
 Atenolol, oral, 50–100 mg daily.
o Contraindicated in asthmatics, heart failure.
If in CCF:
 Carvedilol, oral.
See section 3.4: Congestive cardiac failure.
AND
If control not adequate add:
 Digoxin, oral, start at 0.125 mg daily and adjust according to rate
response and trough plasma level.
o In patients with impaired renal function (eGFR < 60 mL/minute),
consider 0.125 mg daily and adjust according to trough level
monitoring.
o In all patients, digoxin trough level monitoring is required at all
xvi
doses.
LoE:II
If -blockers are contra-indicated, e.g. asthma or severe peripheral vascular
disease:
 Verapamil, oral, 40–120 mg 8 hourly.
o Titrate against ventricular rate (verapamil is negatively inotropic,
xvii
avoid in heart failure due to left ventricular
LoE:III
dysfunction).
If not controlled on these agents, refer to specialist for consideration of
alternative therapy.
Prevention of recurrent paroxysmal atrial fibrillation:
Note: The risk of thromboembolic complications and stroke is similar to that
of patients with persistent or paroxysmal atrial fibrillation and similar
recommendations as to anticoagulation apply.
Only in patients with severe symptoms despite the above measures:
 Amiodarone, oral, 200 mg 8 hourly for 1 week. Specialist initiated.
o Followed by 200 mg 12 hourly for one week
o Thereafter 200 mg daily.
Precautions:
o If on warfarin, halve the dose of warfarin and monitor INR closely,
until INR is stable.
o Avoid concomitant digoxin.
2015
3.14
CHAPTER 3
o
o
CARDIOVASCULAR SYSTEM
Monitor thyroid function every 6 months as thyroid abnormalities
may develop.
Ophthalmological examination every 6 months.
3.3.1.2 ATRIAL FLUTTER
I48
Atrial rate > 250 beats/minute with no flat baseline.
Can be difficult to recognise if 2:1 atrioventricular (AV) block, as the first of
the 2 p waves preceding each QRS complex might be confused with the Twave of the preceding beat. Vagal stimulation might slow the ventricular rate
(usually approximately 150 beats per minute) and make the dysrhythmia
more obvious.
GENERAL MEASURES
Synchronised DC cardioversion, 200 J, after sedation with:
 Midazolam IV, 1–2.5 mg, administered over 2-3 minutes.
o Monitor and repeat dose after 2-3 minutes, as necessary.
o If 200 J fails, use 360 J.
LoE:III
If flutter has been present longer than 48 hours, defer cardioversion until
after 4 weeks’ anticoagulation with warfarin, unless severe symptoms or
heart failure require urgent cardioversion.
MEDICINE TREATMENT
DC cardioversion is the most effective therapy.
Do not use verapamil as it will not convert flutter to sinus rhythm and
may cause serious hypotension.
Anticoagulants if sustained. (See section 3.3.1.1 Atrial fibrillation. Most
consider that the thromboembolic risks in atrial flutter and atrial fibrillation are
similar).
LoE:III
Long-term therapy
Recurrent atrial flutter is an indication for referral as many may be relatively
simply cured by radio-frequency catheter ablation.
3.3.1.3 AV JUNCTIONAL RE-ENTRY TACHYCARDIAS
I47.1
Usually paroxysmal.
Often young patients with normal hearts.
AV nodal re-entry or Atrioventricular re-entry (WPW syndrome).
P waves usually not visible (hidden by QRS complexes).
GENERAL MEASURES
Vagal manoeuvres: The modified Valsalva manoeuvre is the most effective – it
2015
3.15
CHAPTER 3
CARDIOVASCULAR SYSTEM
should be done semi-recumbent with 15 seconds of strain, followed
immediately by supine positioning and passive leg raising.
Carotid sinus massage.
Should be done with the patient supine and as relaxed as possible.
MEDICINE TREATMENT
Initial therapy
If vagal manoeuvres fail:
 Adenosine, rapid IV bolus, 6 mg.
o Follow by a bolus of 10 mL sodium chloride 0.9% to ensure that it
reaches the heart before it is broken down.
o Half life: ± 10 seconds.
o Run the ECG for 1 minute after the injection.
o If 6 mg fails, repeat with 12 mg.
o If this fails, repeat with another 12 mg.
If the medicine reaches the central circulation before it is broken down
the patient will experience flushing, sometimes chest pain, wheezing and
anxiety.
If the tachycardia fails to terminate without the patient experiencing those
symptoms, the medicine did not reach the heart.
If none of the above is effective or if the patient is hypotensive, consider DC
shock.
Note: Adenosine is contraindicated when atrial flutter is the obvious
diagnosis, administration of adenosine can precipitate 1:1 conduction at
ventricular rates 250–360 beats per minute and should be
LoE:III
avoided.
Long term therapy
Teach the patient to perform vagal manoeuvres. Valsalva is the most
effective.
For infrequent, non-incapacitating symptoms:
 Cardio-selective ß–blocker, e.g.:
 Atenolol, oral, 50–100 mg daily.
If asthmatic, without heart failure:
 Verapamil, oral, 40–120 mg 8 hourly.
Verapamil and digoxin are contraindicated in WPW
syndrome.
xviii
LoE:III
REFERRAL
If the patient continues to experience debilitating symptoms refer for
radiofrequency ablation.
2015
3.16
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.3.2 WIDE QRS (VENTRICULAR) TACHYARRHYTHMIAS
I47.1/I47.2
DESCRIPTION
Sustained (> 30 seconds) or non-sustained wide QRS (> 0.12 seconds)
tachycardias.
3.3.2.1 REGULAR WIDE QRS TACHYCARDIAS
Regular wide QRS tachycardias are ventricular until proved otherwise.
Regular wide QRS supraventricular tachycardias are uncommon.
Refer all cases after resuscitation and stabilisation.
Emergency DC cardioversion is mandatory with a full protocol of Cardiopulmonary resuscitation (CPR).
GENERAL MEASURES
CPR.
If no cardiac arrest:
DC cardioversion, 200 J, after sedation with:
 Midazolam IV, 1–2.5 mg, administered over 2-3 minutes.
o Monitor and repeat dose after 2-3 minutes, as necessary.
o If 200 J fails, use 360 J.
LoE:III
If cardiac arrest:
Defibrillate (not synchronised).
MEDICINE TREATMENT
Caution
Never give verapamil or adenosine IV to patients with a wide QRS
xix
tachycardia as this may precipitate ventricular
LoE:III
fibrillation.
DC cardioversion is first line therapy for regular wide QRS tachycardias.
Medicines are needed if ventricular tachycardia (VT) recurs after
cardioversion, or spontaneous termination.
 Amiodarone, IV, 5 mg/kg infused over 30 minutes.
Follow with:
 Amiodarone, oral, 800 mg daily for 7 days.
o Then 600 mg daily for 3 days.
o Titrate to maintenance dose of 200–400 mg daily. Consult specialist
before instituting long term (>than 1week) therapy.
Precautions:
o If on warfarin, halve the dose of warfarin and monitor INR closely,
until INR is stable.
2015
3.17
CHAPTER 3
CARDIOVASCULAR SYSTEM
o Avoid concomitant digoxin.
o Monitor thyroid function every 6 months as thyroid abnormalities may
develop.
o Ophthalmological examination every 6 months.
3.3.2.2 SUSTAINED (> 30 SECONDS) IRREGULAR WIDE QRS
TACHYCARDIAS
These tachycardias are usually due to atrial fibrillation with bundle branch
block, or pre-excitation (WPW syndrome).
If the QRS complexes have a pattern of typical right or left bundle branch block,
with a rate < 170 beats per minute, treat as for atrial fibrillation. See section
3.3.1: Narrow QRS complex (supraventricular) tachycardias.
If the rate is > 170 beats per minute, and/or the complexes are atypical or
variable, the likely diagnosis is WPW syndrome with atrial fibrillation,
conducting via the bypass tract. Treat with DC conversion.
Do not treat with medication.
Verapamil and digoxin may precipitate ventricular fibrillation by increasing
the ventricular rate.
If in doubt as to the nature of a tachycardia, and in all patients with
haemodynamic compromise, DC cardioversion under IV sedation is the
safest option.
DC cardioversion, 200 J, after sedation with:
 Midazolam IV, 1–2.5 mg, administered over 2-3 minutes.
o Monitor and repeat dose after 2-3 minutes, as necessary.
o If 200 J fails, use 360 J.
LoE:III
3.3.2.3 NON-SUSTAINED (< 30 SECONDS) IRREGULAR WIDE
QRS TACHYCARDIAS
These tachycardias are usually ventricular. They are common in acute
myocardial infarction. Check serum potassium level and correct if low.
MEDICINE TREATMENT
 Amiodarone, IV, 5 mg/kg infused over 30 minutes.
Follow with:
 Amiodarone, oral, 800 mg daily for 7 days.
o Then 600 mg daily for 3 days.
o Follow with a maintenance dose of 200–400 mg daily, depending
upon clinical judgement. Consult specialist before instituting long term
(>than 1week) therapy.
Precautions:
o If on warfarin, halve the dose of warfarin and monitor INR closely,
until INR is stable.
2015
3.18
CHAPTER 3
CARDIOVASCULAR SYSTEM
o Avoid concomitant digoxin.
o Monitor thyroid function every 6months as thyroid abnormalities may
develop.
o Ophthalmological examination every 6 months.
OR
Only in haemodynamically stable patients:
 Lidocaine (lignocaine), IV, 50–100 mg (1–2 mg/kg) initially and at 5
minute intervals if required to a total of 200–300 mg.
Thereafter, for recurrent ventricular tachycardia only:
 Lidocaine, IV infusion, 1–3 mg/minute for 24–30 hours.
Lidocaine will only terminate ± 30% of sustained ventricular tachycardias,
and may cause hypotension, heart block or convulsions.
For emergency treatment of ventricular tachycardia, DC cardioversion is first
line therapy, even if stable.
In the absence of acute ischaemia or infarction, consider torsades de
pointes, due to QT prolonging medicines.
3.3.2.4 TORSADES DE POINTES VENTRICULAR
TACHYCARDIA (VT)
Torsades de pointes Ventricular Tachycardia (VT) has a twisting pattern to
the QRS complexes and a prolonged QT interval in sinus rhythm. It is
usually due to a QT-prolonging medication, active myocardial ischaemia
and/or hypokalaemia and/or a history of alcohol abuse/malnutrition.
GENERAL MEASURES
Cardioversion/defibrillation, as necessary.
Torsades complicating bradycardia: temporary pacing.
MEDICINE TREATMENT
Stop all QT-prolonging medicines. (A list of medicines that cause QT
prolongation can be viewed at www.sads.org.uk/drugs_to_avoid.htm).
Correct serum potassium.

Magnesium sulphate, IV, 2 g administered over 5–10 minutes.
If recurrent episodes after initial dose of magnesium sulphate:
 Magnesium sulphate, IV, 2 g administered over 24 hours.
LoE:III
Torsades complicating bradycardia:
 Adrenaline (epinephrine) infusion to raise heart rate to > 100 beats per
minute (if temporary pacing unavailable).
REFERRAL
All cases of wide QRS tachycardia, after resuscitation and stabilization.
2015
3.19
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.3.3 HEART BLOCK (SECOND OR THIRD DEGREE)
I44.1/I44.2
DESCRIPTION
The majority of cases occur in patients > 60 years of age and are idiopathic,
with an excellent long-term prognosis, provided a permanent pacemaker is
implanted. Acute, reversible AV block commonly complicates inferior
myocardial infarction. Heart block may also be induced by metabolic and
electrolyte disturbances, as well as by certain medicines.
GENERAL MEASURES
Emergency cardio-pulmonary resuscitation.
External pacemaker should be available in all secondary hospitals and must
be preceded by appropriate analgesia.
MEDICINE TREATMENT
Analgesia if external pacemaker:
 Morphine, IM, 10–15 mg 3–6 hourly.
Apply relevant precautions as indicated in Appendix II (i.e. monitoring for
response and toxicity).
AV nodal block with narrow QRS complex escape rhythm only:
 Atropine, IV bolus, 0.6–1.2 mg.
o May be repeated as needed until a pacemaker is inserted.
o Use in patients with inferior myocardial infarct and hypotension and
second degree AV block, if symptomatic.
o It is temporary treatment of complete AV block before referral
(urgently) for pacemaker.
OR
For resuscitation of asystole in combination with CPR:
 Adrenaline (epinephrine) 1:10 000, slow IV, 5 mL (0.5 mg).
o
Used as temporary treatment of complete heart block when other
medicines are not effective.
REFERRAL
»
All cases with a heart rate < 40 beats per minute after resuscitation and
stabilization.
nd
rd
» All cases of 2 or 3 degree AV block, whether or not myocardial infarct
or other reversible cause is suspected, and whether or not the patient is
thought to be symptomatic.
A permanent pacemaker is the definitive form of treatment. These are only
available in tertiary institutions. (Refer all symptomatic patients with
significant bradyarrhthmias for evaluation).
2015
3.20
CHAPTER 3
CARDIOVASCULAR SYSTEM
3.3.4 SINUS BRADYCARDIA
I49.8
DESCRIPTION
This rhythm does not require treatment, unless it is causing symptoms, i.e.
syncope, dizziness, tiredness and poor effort tolerance.
Sinus bradycardia < 50 beats per minute or sinus arrest with slow escape
rhythm, accompanied by hypotension, strongly suggest a treatable
underlying cause such as:
» acute inferior myocardial infarct,
» hyperkalaemia, especially if wide QRS and/or peaked T waves,
» medicines, especially combination of verapamil and ß-blocker or digoxin,
» hypothermia,
» hypoxia, or
» hypothyroidism.
Treat the cause. Consider atropine if inferior myocardial infarct.
3.3.5 SINUS ARREST
I45.5
Refer all urgently to a cardiologist.
3.4 CONGESTIVE CARDIAC FAILURE (CCF)
I50.0
DESCRIPTION
CCF is a clinical syndrome and has several causes. The cause and
immediate precipitating factor(s) of the CCF must be identified and treated to
prevent further damage to the heart.
Potentially reversible causes include:
» anaemia
» thyroid disease
» valvular heart disease
» constrictive pericarditis
» hypertension.
»
»
»
»
thiamine deficiency
ischaemic heart disease
haemochromatosis
tachycardia
GENERAL MEASURES
Patient and family education.
Monitor body weight to assess changes in fluid balance.
Limit fluid intake to 1–1.5 L/day if fluid overloaded despite diuretic therapy.
Limit alcohol intake to a maximum 2 drinks per day if at all.
Influenza immunization.
Salt restriction.
Regular exercise within limits of symptoms.
2015
3.21
CHAPTER 3
CARDIOVASCULAR SYSTEM
Avoid NSAIDs as these may exacerbate fluid retention.
Counsel that pregnancy may exacerbate heart failure and some medicines
used in treatment of heart failure are contraindicated in pregnancy e.g. ACExx
inhibitors, angiotensin-receptor blockers, spironolactone.
LoE:III
MEDICINE TREATMENT
Where heart failure is due to left ventricular systolic dysfunction, mortality is
significantly reduced by the use of ACE-inhibitors, ß-blockers and
spironolactone and every effort should be made to ensure eligible patients
receive these agents in appropriate doses.
Digoxin has been shown to improve symptoms and reduce hospitalisation
xxi
only.
LoE:I
Diuretic
Mild volume overload (mild CCF) and normal renal function, thiazide diuretic:
 Hydrochlorothiazide, oral, 25–50 mg daily.
o Caution in patients with gout.
o Less effective in impaired renal function.
Significant volume overload or abnormal renal or hepatic function, loop diuretic:
 Furosemide, oral, daily.
o Initial dose: 40 mg/day.
o Higher dosages may be needed, especially if comorbid renal failure.
o Advise patients to weigh themselves daily and adjust the dose if
necessary.
LoE:III
Note:
» Unless patient is clinically fluid overloaded, reduce the dose of diuretics
before adding an ACE-inhibitor. After introduction of an ACE-inhibitor,
try to reduce diuretic dose and consider a change to
hydrochlorothiazide.
» Routine use of potassium supplements with diuretics is not
recommended. They should be used short term only, to correct
documented low serum potassium level.


ACE-inhibitor, e.g.:
Enalapril, oral, 2.5 mg 12 hourly, titrated to 10 mg 12 hourly.
o In the absence of significant side-effects always try to increase the
xxii
dose to the level shown to improve prognosis
LoE:I
(i.e.10 mg 12 hourly).
If ACE-inhibitor intolerant, i.e. intractable cough:
 Angiotensin receptor blocker (ARB), e.g.:
 Losartan, oral, 50–100 mg daily. (Specialist initiated)
Spironolactone
Use with an ACE-inhibitor and furosemide in patients presenting with Class
III or IV heart failure.
Do not use if eGFR < 30 mL/minute.
2015
3.22
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CARDIOVASCULAR SYSTEM
Monitoring of potassium levels is essential if spironolactone is used with an
ACE-inhibitor or other potassium sparing agent or in the elderly.
 Spironolactone, oral, 25–50 mg once daily.
xxiii
LoE:III
ß-blockers
For all stable patients with heart failure who tolerate it:
Note: Patients should not be fluid overloaded or have a low BP before
initiation of therapy.
 Carvedilol, oral.
o Initial dose: 3.125 mg 12 hourly.
o Increase at 2-weekly intervals by doubling the daily dose until a
maximum of 25 mg 12 hourly, if tolerated.
o If not tolerated, i.e. worsening of cardiac failure symptoms, reduce the
dose to the previously tolerated dose.
o Up-titration should take several weeks or months.
xxiv
LoE:I
Digoxin
Patients remaining symptomatic after the above-mentioned agents
(Specialist consultation):
 Digoxin, oral, 0.125 mg daily, adjust according to rate response and
trough plasma level.
o Digoxin trough plasma levels (before the morning dose) should be
maintained between 0.6-1 nmol/L.
o Patients at high risk of digoxin toxicity are:
 the elderly
 patients with renal dysfunction
 hypokalaemia
xxv
LoE:II
 patients with lean body mass
Anticoagulants
Heparin: for DVT prophylaxis.
For patients admitted to hospital, unless contraindicated:

Unfractionated heparin, SC, 5 000 units 12 hourly.
xxvi
OR


LoE:II
Low molecular weight heparin, e.g.:
Enoxaparin, SC, 40 mg daily.
xxvii
LoE:I
Warfarin: See section 3.3.1: Narrow QRS complex (supraventricular)
tachydysrhythmias.
Anti-dysrhythmic medicines
See section 3.3: Cardiac Dysrhythmias.
Only for potentially life-threatening ventricular dysrythmias.
Always exclude electrolyte abnormalities and medicine toxicity first.
2015
3.23
CHAPTER 3
CARDIOVASCULAR SYSTEM
Thiamine
Consider as a trial of therapy in all unexplained heart failure:
 Thiamine, oral/IM, 100 mg daily for 4 weeks.
REFERRAL
»
»
»
»
Where specialised treatment and diagnostic work-up is needed and to
identify treatable and reversible causes.
All patients with audible cardiac murmurs should undergo specialist
evaluation, as should all patients with potentially reversible causes of the
heart failure syndrome and those with persistent and severe symptoms
and signs of fluid overload despite adequate doses of diuretic.
Patients who have left bundle branch block (LBBB) on the ECG are
potential candidates for cardiac resynchronization therapy. An ECG
should be recorded at baseline and repeated at 6-monthly intervals.
Patients with LBBB should be referred for consideration for
resynchronsation therapy, discussed with a specialist.
3.5 ENDOCARDITIS, INFECTIVE
I09.1
GENERAL MEASURES
Bed rest.
Early surgical intervention in acute fulminant and prosthetic valve endocarditis
is often indicated. Surgery should also be considered if there is heart failure,
embolism, large vegetations on echocardiography, heart block, evidence of
persistent infection despite antibiotics or renal impairment. Refer these
patients promptly.
LoE:III
MEDICINE TREATMENT
Treat accompanying complications, e.g. cardiac failure. Such treatment
should not delay referral.
Antibiotic therapy
It is essential to do at least 3 blood cultures, taken by separate
venipunctures, before starting antibiotics.
In patients with subacute presentation and no haemodynamic compromise,
wait for the results of blood culture before starting antibiotics.
Empiric treatment is indicated in patients with a rapidly fulminant course or
with severe disease only.
Aminoglycoside therapy should be monitored with trough levels for safety.
Duration of therapy given is the minimum and may be extended based on
the response (clinical and laboratory).
Severe penicillin-allergic patients, or methicillin resistant staphylococcal
infections:

Vancomycin, IV, 20 mg/kg 12 hourly, is the antibiotic of choice. It is
2015
3.24
CHAPTER 3
CARDIOVASCULAR SYSTEM
essential to monitor trough concentrations of vancomycin regularly and
adjust doses accordingly, starting after the third dose.
xxviii
LoE:III
Empiric therapy

Benzylpenicillin (penicillin G), IV, 5 million units
Native valve
6 hourly for 4 weeks
AND

Gentamicin, IV, 1.5 mg/kg 12 hourly for 2 weeks
If staphylococcal infection is suspected (acute onset):
ADD

Cloxacillin, IV, 3 g 6 hourly.

Vancomycin, IV, 20 mg/kg 12 hourly for 6 weeks.
Prosthetic
AND
valve*

Rifampicin, oral, 7.5 mg/kg 12 hourly for 6 weeks.
AND

Gentamicin, IV, 1.5 mg/kg 12 hourly for 2 weeks.
* All cases of prosthetic valve endocarditis should be referred.
Directed therapy (native valve)
Streptococcal
Fully susceptible
to penicillin
MIC: < 0.2mg/L

Moderately
susceptible
MIC: 0.12–0.5
mg/L

Moderately
resistant
MIC: 0.5–4mg/L
Enterococci and
Abiotrophia spp.
(nutritionally
variant
streptococci)

Fully resistant
MIC: > 4 mg/L
 Vancomycin, IV, 20 mg/kg 12 hourly for 6 weeks.
AND
 Gentamicin, IV, 1.5 mg/kg 12 hourly for 6 weeks.
Benzylpenicillin (penicillin G), IV, 5 million units
6 hourly for 4 weeks.
Benzylpenicillin (penicillin G), IV, 5 million units
6 hourly for 4 weeks.
AND
 Gentamicin, IV, 1.5 mg/kg 12 hourly for 2 weeks.
Benzylpenicillin (penicillin G), IV, 5 million units
6 hourly for 4 weeks.
AND
 Gentamicin, IV, 1.5 mg/kg 12 hourly for 4 weeks.
Six weeks of therapy may be required in cases
with a history of > 3 months, or mitral or prosthetic
valve involvement.
Enterococcal
Fully susceptible
to penicillin
MIC: < 4mg/L
2015

Benzylpenicillin (penicillin G), IV, 5 million units
6 hourly for 4 weeks.
3.25
CHAPTER 3
CARDIOVASCULAR SYSTEM
Resistant to
penicillin
MIC ≥4mg/L or
significant lactam allergy
and
Sensitive to
vancomycin MIC:
≤4 mg/L
Refer.
Staphylococcal (cloxacillin/methicillin sensitive)
S. aureus
 Cloxacillin, IV, 3 g 6 hourly for 4 weeks.
If necessary, add:
 Gentamicin, IV, 6 mg/kg daily for the first
3–5 days.
The benefit of adding an aminoglycoside has not
been established.
In the rare occurrence of a penicillin sensitive
staphylococcus, penicillin should be used in
preference to cloxacillin.
Coagulasenegative
staphylococci
Consult expert opinion on correct diagnosis in this
setting.
Staphylococcal (cloxacillin/methicillin resistant) or methicillin
sensitive with significant beta-lactam allergy
S. aureus
Coagulasenegative
staphylococci

Vancomycin, IV, 20 mg/kg 12 hourly for 4 weeks.
Consult expert on correct on antibiotic choice.
Directed therapy for prosthetic valve endocarditis
Duration of therapy is usually a minimum of at least 6 weeks.
Seek expert opinion on antibiotic choice.
Endocarditis prophylaxis
Cardiac conditions
Patients with the following cardiac conditions are at high risk of developing
infective endocarditis:
» Acquired valvular heart disease with stenosis or regurgitation.
» Patients with prosthetic heart valves.
» Structural congenital heart disease, including surgically corrected or
palliated structural conditions, but excluding isolated atrial septal defect,
fully repaired ventricular septal defect or fully repaired patent ductus
2015
3.26
CHAPTER 3
CARDIOVASCULAR SYSTEM
arteriosus.
Patients who have suffered previous endocarditis.
»
Procedures requiring prophylaxis
Antibiotic prophylaxis is recommended for all dental procedures that involve
manipulation of either the gingival tissue or the peri-apical region of the teeth.
Antibiotic prophylaxis is not recommended for patients who undergo a
gastro-intestinal or genito-urinary procedure.
Prophylaxis
Maintain good dental health.
This is the most important aspect of prophylaxis.
Refer all patients to a dental clinic/dental therapist for assessment and ongoing dental care.

Amoxicillin, oral, 2 g one hour before the procedure.
If patient cannot take oral:
 Ampicillin, IV/IM, 2 g one hour before the procedure.
Severe penicillin allergy:
 Clindamycin, oral, 600 mg one hour before the procedure.
If patient cannot take oral:
 Clindamycin IV, 600 mg one hour before the procedure.
The NICE review noted the lack of a consistent association between
interventional procedures and development of infective endocarditis, and
that the efficacy of antibiotic prophylaxis is unproven. It further commented
that because the antibiotic is not without risk, there is a potential for a greater
mortality from severe hypersensitivity than from withholding antibiotics.
It is very difficult to extrapolate from these guidelines to a South African
situation where good dental hygiene may be lacking and valvular heart
disease is common. Practitioners need to weigh the risk of the underlying
heart disease (particularly previous successfully treated endocarditis) and
the essential need for ongoing antibiotic stewardship.
xxix
LoE:III
3.6 HYPERTENSION
I10
KEY POINTS
Hypertension control has significant benefit for patients.
Detect and treat co-existent risk factors.
Assess cardiovascular risk.
Lifestyle modification and patient education is essential for all patients.
2015
3.27
CHAPTER 3
CARDIOVASCULAR SYSTEM
Medicine treatment is needed for SBP > 140 mmHg and DBP > 90 mmHg
despite lifestyle modification.
See medicine treatment choices below.
Immediate medicine treatment is needed for DBP ≥ 110 mmHg and/or SBP
≥ 180 mmHg (defined as severe hypertension - see sections 3.6.1, 3.6.2
and 3.6.3) or for patients with 3 or more risk factors, target organ damage
and/or associated clinical conditions.
Patients should be evaluated for cardiovascular risk factors, target
organ damage and associated clinical conditions.
Other major risk factors for ischaemic cardio- and cerebrovascular disease
(see section 3.1).
Target organ damage:
» left ventricular hypertrophy,
» hypertensive retinopathy
» microalbuminuria, or
» elevated creatinine level.
Associated clinical conditions:
» ischaemic heart disease,
» heart failure,
» stroke or transient ischaemic attack,
» chronic kidney disease,
» peripheral arterial disease.
Investigations
If overweight, record body weight and waist circumference at each visit when
BP is measured. Central obesity is defined as waist circumference:
» 102 cm in men, and
» 88 cm in women.
Do urine test strip analysis for protein, blood and glucose at presentation.
» If normal, repeat urine test strip every 6 months.
» If abnormal, do spot urine albumin:creatinine ratio. Repeat yearly.
» If haematuria > 1+, investigate further.
» If glycosuria, exclude diabetes mellitus.
» If known diabetic, HbA1c.
» Random total cholesterol.
» Perform a resting ECG to exclude left ventricular hypertrophy or ischaemia.
» Assess renal function (serum creatinine and eGFR).
Goals of treatment
Aim for SBP < 140 mmHg and DBP < 90 mmHg.
2015
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CHAPTER 3
CARDIOVASCULAR SYSTEM
GENERAL MEASURES
Lifestyle modification
All persons with hypertension should be encouraged to make the following
lifestyle changes as appropriate.
» Smoking cessation.
2
» Maintain ideal weight, i.e. BMI < 25 kg/m . Weight reduction in the
overweight patient.
» Salt restriction with increased potassium intake from fresh fruits and
vegetables (e.g. remove the salt from the table, gradually reduce added
salt in food preparation and avoid processed foods).
» Reduce alcohol intake to no more than 2 standard drinks per day for
males and 1 for females.
» Follow a prudent eating plan i.e. low fat, high fibre and unrefined
carbohydrates, with adequate fresh fruit and vegetables.
» Regular moderate aerobic exercise, e.g. 40 minutes brisk walking at
least 3 times a week.
MEDICINE TREATMENT
Initial medicine choice in patients qualifying for treatment is dependent on
the presence of compelling indications (see table on page 3.31); the severity
of the BP; and the presence of target organ damage, cardiovascular risk
factors, and associated clinical conditions.
Advise patient to take medication regularly, including on the day of the
clinic visit.
Note:
» Check adherence to antihypertensive therapy.
» Monitor patients monthly and adjust therapy if necessary until the BP is
controlled.
» After target BP is achieved, patients can be seen at 3–6 monthly
intervals.
Medicine treatment choices without compelling indications
BP 140-159/90-99 mmHg, < 3 risk factors, no target organ damage or
associated clinical conditions:
» Lifestyle modification for 3–6 months.
» Start antihypertensive therapy with a single medicine if target BP not
achieved.
» Start antihypertensive therapy immediately (together with lifestyle
modification) if there are 3 or more risk factors, target organ damage
and/or associated clinical conditions.
BP 160-179/100-109 mmHg, < 3 risk factors, no target organ damage or
associated clinical conditions:
» Lifestyle modification for 3–6 months.
2015
3.29
CHAPTER 3
»
CARDIOVASCULAR SYSTEM
Start antihypertensive therapy with a combination of two medicines if
target BP not achieved.
Start antihypertensive therapy immediately (together with lifestyle
modification) if there are 3 or more risk factors, target organ damage
and/or associated clinical conditions.
»
BP ≥180/100 mmHg: this is severe hypertension – see sections 3.6.1, 3.6.2
and 3.6.3.
Initial antihypertensive medicine:
 Low dose thiazide diuretic e.g.:
 Hydrochlorothiazide, oral, 12.5 mg daily.
If target BP is not reached after one month despite adequate adherence (or
immediately in patients with BP 160-179/100-109 mmHg), add one of the
following: ACE-inhibitor or calcium channel blocker.
 ACE-inhibitor, e.g.:
 Enalapril, oral, 10 mg daily.
OR
 Long-acting calcium channel blocker, e.g.:
 Amlodipine, oral, 5 mg daily.
If target BP is not reached after one month despite adequate adherence on
two medicines, add one of ACE-inhibitor or calcium channel blocker,
whichever has not already been used.
If target BP is not reached after one month despite adequate adherence,
add a β-blocker.


β -blocker , e.g.:
Atenolol, oral, 50 mg daily.
If target BP is not achieved after one month despite adequate adherence,
increase the dose of medication, one medicine every month, to their maximal
levels: enalapril 10 mg 12 hourly, amlodipine 10 mg daily and
hydrochlorothiazide 25 mg daily.
Note: In 60–80% of patients a combination of the above antihypertensive
therapy is needed. Combination therapy, i.e. hydrochlorothiazide plus a
calcium channel blocker or ACE-inhibitor should be considered at the outset
in patients with BP > 160/100 mmHg.
2015
3.30
CHAPTER 3
CARDIOVASCULAR SYSTEM
Medicine treatment choices with compelling indications
Compelling indications
Angina
Medicine class
ß-blocker
Calcium channel blocker
Post myocardial infarction
ß-blocker
ACE-inhibitor
Heart failure
ACE-inhibitor
Carvedilol
Spironolactone
Hydrochlorothiazide or furosemide
Left ventricular hypertrophy
ACE-inhibitor
Stroke
Hydrochlorothiazide
ACE-inhibitor
Diabetes type 1 or 2 with/without
evidence of microalbuminuria or
proteinuria
ACE- inhibitor, usually in combination with
a diuretic
Chronic kidney disease
ACE-inhibitor, usually in combination with
a diuretic
Isolated systolic hypertension
Hydrochlorothiazide
Calcium channel blocker
Pregnancy
See Chapter 6: Obstetrics.
Caution
Lower BP over a few days.
A sudden drop in BP can be dangerous, especially in the elderly.
BP should be controlled within 1–6 months.
Risk assessment: 10 year risk of MI > 20%:
 HMGCoA reductase inhibitors e.g.:
xxx
LoE:I
 Simvastatin, oral, 10 mg at night.
This therapy requires good initial evaluation, ongoing
support for patients and continuous evaluation to ensure compliance.
Therapy should be initiated together with appropriate lifestyle
modification and adherence monitoring.
See section 3.1: Ischaemic heart disease and atherosclerosis, prevention.
REFERRAL
Referrals or consultation with a specialist are indicated when:
» Patients are adherent to therapy, and BP is refractory, i.e. >140/90
2015
3.31
CHAPTER 3
CARDIOVASCULAR SYSTEM
mmHg, while on medicines from 3–4 different classes at appropriate
dose, one of which is a diuretic.
All cases where secondary hypertension is suspected.
Complicated hypertensive urgency e.g. malignant/accelerated
hypertension, severe heart failure with hypertension and hypertensive
emergency.
»
»
3.6.1 HYPERTENSION, ASYMPTOMATIC SEVERE
DESCRIPTION
These patients have severe hypertension (DBP ≥ 110 mmHg and/or SBP
≥180 mmHg), are asymptomatic and have no evidence of progressive target
organ damage.
Keep the patient in the care setting and repeat BP measurement after
resting for 1 hour.
nd
If the 2 measurement is still elevated at the same level, start oral therapy
using 2 medicines together, one of which should be low dose
nd
hydrochlorothiazide. The 2 medicine is either a long-acting calcium
channel blocker, e.g. amlodipine, or an ACE-inhibitor, e.g. enalapril.
Follow up carefully and refer as needed.
3.6.2 HYPERTENSIVE URGENCY
DESCRIPTION
Severe hypertension (DBP ≥ 110 mmHg and/or SBP ≥180 mmHg) which is
symptomatic and/or with evidence of progressive target organ damage.
There are no immediate life threatening neurological or cardiac
complications such as are seen in the hypertensive emergencies.
Do not lower BP in acute stroke or use antihypertensive medication
unless SBP > 220 mmHg or the DBP > 120 mmHg, as a rapid fall in BP
may aggravate cerebral ischaemia and worsen the stroke.
Treatment may be given orally but in patients unable to swallow, use
parenteral medicines.
MEDICINE TREATMENT
Ideally, all patients with hypertensive urgency should be treated in hospital.
Commence treatment with 2 oral agents and aim to lower the DBP to 100
mmHg slowly over 48–72 hours.
This BP lowering can be achieved by:
 Long-acting calcium channel blocker.
 ACE-inhibitor.
Note: Avoid if there is severe hyponatraemia, i.e. serum Na < 130 mmol/L.
2015
3.32
CHAPTER 3

CARDIOVASCULAR SYSTEM
-blocker.
Diuretics may potentiate the effects of the other classes of medicines when
added. Furosemide should be used if there is renal insufficiency or signs of
pulmonary congestion.
3.6.3 HYPERTENSIVE CRISIS, HYPERTENSIVE
EMERGENCY
DESCRIPTION
This is a life-threatening situation that requires immediate lowering of BP
usually with parenteral therapy. Grade 3-4 hypertensive retinopathy is
usually present, together with impaired renal function and proteinuria.
The true emergency situation should preferably be treated by a specialist.
Life-threatening complications include:
» Hypertensive encephalopathy, i.e. severe headache, visual
disturbances, confusion, seizures and coma that may result in cerebral
haemorrhage.
» Unstable angina or myocardial infarction.
» Acute left ventricular failure with severe pulmonary oedema (extreme
breathlessness at rest).
» Eclampsia and severe pre-eclampsia.
» Acute kidney failure with encephalopathy.
» Acute aortic dissection.
MEDICINE TREATMENT
Admit the patient to a high-care setting for intravenous therapy and close
monitoring. Do not lower the BP by > 25% within 30 minutes to 2 hours.
In the next 2–6 hours, aim to decrease the BP to 160/100 mmHg.
This may be achieved by the use of intravenous or oral medicines.
Intravenous therapy
 Labetalol, IV, 2 mg/minute to a total dose of 1–2 mg/kg, while trying to
achieve control with other agents.
o Caution in acute pulmonary oedema.
OR
If myocardial ischaemia and CCF:
 Glyceryl trinitrate, IV, 5–10 mcg/minute.
Refer to dosing table in section 3.2.1: ST elevation myocardial infarction
(STEMI).

Furosemide, IV, 40–80 mg.
o Duration of action: 6 hours.
o Potentiates all of the above medicines.
2015
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CHAPTER 3
CARDIOVASCULAR SYSTEM
Oral therapy
 ACE-inhibitor, e.g.:
 Enalapril, oral, 2.5 mg as a test dose
o Increase according to response, to a maximum of 20 mg daily.
o Monitor renal function.
3.7 RHEUMATIC HEART DISEASE
I09.9
DESCRIPTION
These are chronic sequelae of rheumatic fever consisting of valvular
damage, usually involving left heart valves, with progression and
complications.
GENERAL MEASURES
Acute stage of rheumatic fever: bed rest and supportive care.
.
MEDICINE TREATMENT
Acute rheumatic fever
For eradication of streptococci in throat:
 Benzathine benzylpenicillin (depot formulation), IM, 1.2 million units as a
single dose.
o For benzathine benzylpenicillin, IM injection, dissolve benzathine
benzylpenicillin 1.2 MU in 3.2 mL lidocaine 1% without
xxxi
adrenaline (epinephrine) or 3 mL water for injection.
LoE:III
OR
Phenoxymethylpenicillin, oral, 500 mg 12 hourly for 10 days.
Severe penicillin allergy:
 Macrolide, e.g.:
 Azithromycin, oral, 500 mg daily for 3 days.
For arthritis and fever:
 NSAIDs, e.g:
 Ibuprofen, oral, 400 mg 8 hourly with meals.
xxxii
LoE:I
LoE:III
Prevention of recurrent rheumatic fever
All patients with confirmed rheumatic fever and no persistent rheumatic
valvular disease:
» Treat for 10 years or until the age of 21 years, whichever is longer.
All patients with confirmed rheumatic fever and persistent rheumatic valvular
disease:
xxxiii
» Treat lifelong.
LoE:III
 Benzathine benzylpenicillin (depot formulation), IM, 1.2
2015
3.34
CHAPTER 3
CARDIOVASCULAR SYSTEM
million units every 3–4 weeks (preferred treatment).
o For benzathine benzylpenicillin, IM injection, dissolve benzathine
benzylpenicillin 1.2 MU in 3.2 mL lidocaine 1% without adrenaline
(epinephrine).
xxxiv
OR
LoE:III
Phenoxymethylpenicillin, oral, 250 mg 12 hourly.


Severe penicillin allergy:
Azithromycin, oral, 250 mg daily.
LoE:III
Prophylaxis for infective endocarditis
See section 3.5: Endocarditis, infective.
REFERRAL
»
»
Any patient with rheumatic valvular heart disease who requires a
significant dose of diuretic to control fluid overload should be discussed
with a specialist for possible valve surgery.
Pregnancy.
References:
i
Risk factors for prevention of ischaemic heart disease and atherosclerosis (psychological stress): Yusuf S,
Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L;
INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction
in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52.
http://www.ncbi.nlm.nih.gov/pubmed/15364185
ii
de Vries FM, Kolthof J, Postma MJ, Denig P, Hak E. Efficacy of standard and intensive statin treatment for the
secondary prevention of cardiovascular and cerebrovascular events in diabetes patients: a meta-analysis. PLoS
One. 2014 Nov 5;9(11):e111247. http://www.ncbi.nlm.nih.gov/pubmed/25372483
iii
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
iv
Clopidogrel (STEMI): Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS; COMMIT
(Clopidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in
45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005 Nov
5;366(9497):1607-21. http://www.ncbi.nlm.nih.gov/pubmed/16271642
Clopidogrel (STEMI): Contract circular HP09-2014SD. http://health.gov.za/
v
Thrombolytics (Therapeutic class): Dundar Y, Hill R, Dickson R, Walley T. Comparative efficacy of thrombolytics
in acute myocardial infarction: A systematic review. QJM - Monthly Journal of the Association of Physicians.
2003;96(2):103-13. http://www.ncbi.nlm.nih.gov/pubmed/12589008
Thrombolytics (Therapeutic class): National Department of Health: Affordable Medicines, EDP-Adult Hospital
level. Medicine Review: Thrombolytics, therapeutic class for STEMI, July 2015.
http://www.health.gov.za/
vi
Streptokinase: Squire IB, Lawley W, Fletcher S, Holme E, Hillis WS, Hewitt C, Woods KL. Humoral and cellular
immune responses up to 7.5 years after administration of streptokinase for acute myocardial infarction. Eur Heart J.
1999 Sep;20(17):1245-52. http://www.ncbi.nlm.nih.gov/pubmed/10454976
Streptokinase: Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic treatment in acute
myocardial infarction: reappraisal of the golden hour. Lancet. 1996 Sep 21;348(9030):771-5.
http://www.ncbi.nlm.nih.gov/pubmed/8813982
vii
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
2015
3.35
CHAPTER 3
CARDIOVASCULAR SYSTEM
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
viii
Clopidogrel (NSTEMI): Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable
Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with
acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502. Erratum in:
N Engl J Med 2001 Dec 6;345(23):1716. N Engl J Med 2001 Nov 15;345(20):1506.
http://www.ncbi.nlm.nih.gov/pubmed/11519503
Clopidogrel (NSTEMI): Yusuf S, Mehta SR, Zhao F, Gersh BJ, Commerford PJ, Blumenthal M, Budaj A,
Wittlinger T, Fox KA; Clopidogrel in Unstable angina to prevent Recurrent Events Trial Investigators. Early and late
effects of clopidogrel in patients with acute coronary syndromes. Circulation. 2003 Feb 25;107(7):966-72.
http://www.ncbi.nlm.nih.gov/pubmed/12600908
Clopidogrel (NSTEMI): Contract circular HP09-2014SD. http://health.gov.za/
ix
Parenteral anticoagulation (NSTEMI, UA): Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N,
Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. CochraneDatabase Syst Rev.
2014 Jun 27;6:CD003462. http://www.ncbi.nlm.nih.gov/pubmed/24972265
Parenteral anticoagulation (NSTEMI, UA): Ferguson JJ, Califf RM, Antman EM, Cohen M, Grines CL, Goodman
S, Kereiakes DJ, Langer A, Mahaffey KW, Nessel CC, Armstrong PW, Avezum A, Aylward P, Becker RC, Biasucci
L, Borzak S, Col J, Frey MJ, Fry E, Gulba DC, Guneri S, Gurfinkel E, Harrington R, Hochman JS, Kleiman NS,
Leon MB, Lopez-Sendon JL, Pepine CJ, Ruzyllo W, Steinhubl SR, Teirstein PS, Toro-Figueroa L, White H;
SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment
elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the
SYNERGY randomized trial. JAMA. 2004 Jul 7;292(1):45-54. http://www.ncbi.nlm.nih.gov/pubmed/15238590
Parenteral anticoagulation (NSTEMI, UA): Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ,
Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi F. A comparison of low-molecular-weight
heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous
Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997 Aug 14;337(7):447-52.
http://www.ncbi.nlm.nih.gov/pubmed/9250846
Parenteral anticoagulation (NSTEMI, UA): Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG,
Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED,
Sabatine MS, Smalling RW, Zieman SJ; American College of Cardiology; American Heart Association Task Force
on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons;
American Association for Clinical Chemistry. 2014 AHA/ACC Guideline for the Management of Patients with NonST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23;64(24):e139-228.
http://www.ncbi.nlm.nih.gov/pubmed/25260718
x
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
xi
Enalapril: SAMF, 2014
xii
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
xiii
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
2015
3.36
CHAPTER 3
CARDIOVASCULAR SYSTEM
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
xiv
Digoxin: Fauchier L, Laborie G, Clementy N, Bernard A, Angoulvant D, Lip GHY, Babuty D. Effect of digoxin on
all-cause mortality in patients with atrial fibrillation in a population-based cohort study. Heart Failure Congress; May
24, 2015; Seville, Spain. Presentation 539. https://www.escardio.org/
Digoxin: Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin
concentration and outcomes in patients with heart failure. JAMA. 2003 Feb 19;289(7):871-8.
http://www.ncbi.nlm.nih.gov/pubmed/12588271
Digoxin: SAMF, 2014.
xv
Verapamil: SAMF, 2014.
xvi
Digoxin: Fauchier L, Laborie G, Clementy N, Bernard A, Angoulvant D, Lip GHY, Babuty D. Effect of digoxin on
all-cause mortality in patients with atrial fibrillation in a population-based cohort study. Heart Failure Congress; May
24, 2015; Seville, Spain. Presentation 539. https://www.escardio.org/
Digoxin: SAMF, 2014.
xvii
Verapamil: SAMF, 2014.
xviii
Verapamil: SAMF, 2014.
xix
Adenosine: SAMF, 2014.
Verapamil: SAMF, 2014.
xx
Pregnancy – medicines contraindicated: SAMF, 2014.
xxi
Digoxin: Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart
failure. N Engl J Med. 1997 Feb 20;336(8):525-33. http://www.ncbi.nlm.nih.gov/pubmed/9036306
xxii
Enalapril target dose: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and
congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991 Aug 1;325(5):293-302.
http://www.ncbi.nlm.nih.gov/pubmed/2057034
Enalaprol target dose: Effect of enalapril on mortality and the development of heart failure in asymptomatic
patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. N Engl J Med. 1992 Sep
3;327(10):685-91. Erratum in: N Engl J Med 1992 Dec 10;327(24):1768.
http://www.ncbi.nlm.nih.gov/pubmed/1463530
xxiii
Spironolactone: SAMF, 2014.
xxiv
Carvedilol: Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne
A, Roecker EB, Schultz MK, DeMets DL; Carvedilol Prospective Randomized Cumulative Survival Study Group.
Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8.
http://www.ncbi.nlm.nih.gov/pubmed/11386263
xxv
Digoxin: Fauchier L, Laborie G, Clementy N, Bernard A, Angoulvant D, Lip GHY, Babuty D. Effect of digoxin on
all-cause mortality in patients with atrial fibrillation in a population-based cohort study. Heart Failure Congress; May
24, 2015; Seville, Spain. Presentation 539. https://www.escardio.org/
Digoxin: Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin
concentration and outcomes in patients with heart failure. JAMA. 2003 Feb 19;289(7):871-8.
http://www.ncbi.nlm.nih.gov/pubmed/12588271
Digoxin: SAMF, 2014.
xxvi
Unfractionated heparin (dosing): Phung OJ, Kahn SR, Cook DJ, Murad MH. Dosing frequency of unfractionated
heparin thromboprophylaxis: a meta-analysis. Chest. 2011 Aug;140(2):374-81.
http://www.ncbi.nlm.nih.gov/pubmed/21349929
xxvii
Enoxaparin: Wein L, Wein S, Haas SJ, Shaw J, Krum H. Pharmacological venous thromboembolism
prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007
Jul 23;167(14):1476-86. http://www.ncbi.nlm.nih.gov/pubmed/17646601
xxviii
Vancomycin, IV: Groote Schuur Hospital’s vancomycin protocol.
xxix
Antibiotics for prophylaxis (infective endocardtis): NICE, Clinical guideline 64 Prophylaxis against infective
endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing
interventional procedures, March 2008. www.nice.org.uk/CG064
xxx
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
xxxi
Lidocaine 1%: Amir J, Ginat S, Cohen YH, Marcus TE, Keller N, Varsano I. Lidocaine as a diluent for
administration
of
benzathine
penicillin
G.
Pediatr
Infect
Dis
J.
1998
Oct;17(10):890-3.
http://www.ncbi.nlm.nih.gov/pubmed/9802630
xxxii
Azithromycin: van Driel ML, De Sutter AI, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for
group A streptococcal pharyngitis. Cochrane Database Syst Rev. 2013 Apr 30;4:CD004406.
http://www.ncbi.nlm.nih.gov/pubmed/23633318
Azithromycin: SAMF, 2014.
2015
3.37
CHAPTER 3
CARDIOVASCULAR SYSTEM
Azithromycin: Guo D, Cai Y, Chai D, Liang B, Bai N, Wang R. The cardiotoxicity of macrolides: a systematic
review. Pharmazie. 2010 Sep;65(9):631-40. Review. http://www.ncbi.nlm.nih.gov/pubmed/21038838
Azithromycin: Contract circular HP02-2013AI, to 31July2015. http://www.health.gov.za/
xxxiii
Period of antibiotic prophylaxis therapy:Begs S, Petrson G, Thompson A. Report for the 2 nd meeting of the
World Health Organization’s subcommittee of the Expert Committee of the selection and use of essential
medicines: Antibiotic use for the prevention and treatment of rheumatic fever and treatment of rheumatic fever and
rheumatic heart disease in children. 30 June 2008.
http://www.who.int/selection_medicines/committees/subcommittee/2/RheumaticFever_review.pdf
Period of antibiotic prophylaxis therapy: Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman
ST, Taubert KA. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a
scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease
Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional
Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research:
endorsed by the American Academy of Pediatrics. Circulation. 2009 Mar 24;119(11):1541-51.
http://www.ncbi.nlm.nih.gov/pubmed/19246689
xxxiv
Lidocaine 1%: Amir J, Ginat S, Cohen YH, Marcus TE, Keller N, Varsano I. Lidocaine as a diluent for
administration of benzathine penicillin G. Pediatr Infect Dis J. 1998 Oct;17(10):890-3.
http://www.ncbi.nlm.nih.gov/pubmed/9802630
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DERMATOLOGY
Extemporaneous compounding of some of the preparations listed should
only take place at institutions where the competencies and equipment are
available.
4.1 ACNE
L70
DESCRIPTION
Acne is an inflammatory condition of the pilosebaceous unit. Secondary
changes can lead to scarring and inflammation.
Mild acne:
Predominantly consists of non-inflammatory comedones.
Moderate acne:
Consists of a mixture of non-inflammatory comedones and inflammatory
papules and pustules.
Severe acne
It is characterized by the presence of widespread nodules and cysts, as well
as a preponderance of inflammatory papules and pustules.
GENERAL MEASURES
Do not squeeze lesions.
Avoid greasy or oily topical products such as moisturisers that block the hair
follicle openings.
Discourage excessive facial washing.
MEDICINE TREATMENT

Benzoyl peroxide 5%, gel, apply in the morning to affected areas as
tolerated.
o
Wash off in the evening.
o
If ineffective and tolerated, increase application to 12 hourly.
Avoid contact with eyes, mouth, angles of the nose and mucous
i
membranes.
LoE:III
OR
Topical retinoids
Indicated in non-inflammatory acne and where benzoyl peroxide alone is
ineffective.
2015
4.1
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DERMATOLOGY
The main action is to control comedone formation.
Introduce topical retinoids gradually as a night-time application to limit skin
irritant effects, as thery are not photo-stable and degrade when exposed to
sunlight.
Do not use topical retinoids in pregnant women.

Tretinoin, topical, apply at night to affected areas for at least 6 weeks.
o
Review patient after 6 weeks’ treatment.
o
Minimise exposure to UV light.
o
Acne may worsen during the first few weeks.
Moderate Acne:
Topical treatments as above
AND
For inflammatory acne:

Doxycycline, oral, 100 mg daily for 3 months.
o
Review patient after 3 months of treatment.
o
Take with meals.
o
Do not take it with iron preparations and antacids.
ii
LoE:III
Women who need oral contraception and have inflammatory acne can be
initiated on a cyproterone acetate containing combined oral contraceptive
pill.

Cyproterone acetate 2 mg plus ethinyl estradiol 35 mcg, oral, provided
that there is no personal or family history of breast cancer or
thrombosis.
iii
LoE:I
For all severe cases discuss with a dermatologist
4.2 CELLULITIS AND ERYSIPELAS
L03.9/A46
DESCRIPTION
Skin and subcutaneous infections with pain, swelling and erythema usually
caused by streptococci and staphylococci, and occasionally other
organisms. Regional lymphadenitis may be present. Erysipelas has a raised
demarcated border, whilst the border is indistinct in cellulitis.
The presence of areas of necrosis, haemorrhage, or pain out of proportion to
the physical signs should raise suspicion of necrotising fasciitis which
requires aggressive surgical debridement and broad spectrum antibiotics
(e.g. amoxicillin/clavulanic acid) as these infections are often polymicrobial.
2015
4.2
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DERMATOLOGY
GENERAL MEASURES
Elevate the affected limb to reduce swelling.
MEDICINE TREATMENT
For pain:

Ibuprofen, oral, 400 mg 8 hourly with meals.
OR

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
Antibiotic therapy
If intravenous antibiotics are given initially, patients should be switched to
oral agents as soon as there is clinical improvement.
Antibiotics should usually be given for 5–10 days, depending on clinical
response.

Cloxacillin, IV, 1 g 6 hourly.
When there is clinical improvement, change to:

Flucloxacillin, oral, 500 mg 6 hourly.
Severe penicillin allergy:

Clindamycin, IV, 600 mg 8 hourly.
When there is clinical improvement, change to:

Clindamycin, oral, 450 mg 8 hourly.
If patient is admitted and bed-bound with lower limb cellulitis, consider deep
venous thrombosis prophylaxis. See section 2.14 Venous thrombo-embolism.
REFERRAL
Urgent
» For debridement if necrotising fasciitis is suspected, i.e. gangrene, gas
in the tissues or haemorrhagic bullae.
Non-urgent
» To surgeon for non-response.
4.3 IMPETIGO
L01.0
DESCRIPTION
Superficial skin infection, starting as vesicles with an inflammatory halo.
Later a characteristic honey-coloured crust on erythematous base develops
which heals without scarring. Usually caused by group A streptococci or
staphylococci. Post-streptococcal glomerulonephritis is a potential
2015
4.3
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DERMATOLOGY
complication.
GENERAL MEASURES
Good personal and household hygiene to avoid spreading the infection and
to reduce carriage of organisms.
Wash and soak lesions in soapy water to soften and remove crusts.
MEDICINE TREATMENT
Antibiotic therapy

Flucloxacillin, oral, 500 mg 6 hourly for 5 days.
Severe penicillin allergy:

Macrolide, e.g.:

Azithromycin, oral, 500 mg daily for 3 days.
iv
LoE:III
4.4 FURUNCLES AND ABSCESSES
L02.9
DESCRIPTION
Localised bacterial skin infection of hair follicles (furuncle/boil) or dermis
(abscess), usually with S. aureus.
The surrounding skin becomes:
» swollen,
» red,
» hot , and
» tender to touch.
Note: Boils in diabetic, malnourished or other immunocompromised patients
are more likely to develop complications. Check blood glucose levels and
HIV status, if the boils are recurrent.
GENERAL MEASURES
Drainage of the abscess is the treatment of choice. Perform surgical incision
only if the lesion is fluctuant.
The treatment of choice for small furuncles is moist hot compress.
Large fluctuant lesions should be treated with incision and drainage.
Systemic antibiotics are used only as indicated below.
MEDICINE TREATMENT
Antibiotic therapy
Systemic antibiotics are seldom necessary, except if there are:
Facial abscess, or if the abscess is associated with tender draining lymph
nodes, fever, or extensive surrounding cellulitis.
Antibiotics should usually be given for 5–10 days, depending on clinical
response.

Cloxacillin, IV, 1 g 6 hourly.
2015
4.4
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DERMATOLOGY
When there is clinical improvement, change to:

Flucloxacillin, oral, 500 mg 6 hourly.
Severe penicillin allergy:

Clindamycin, IV, 600 mg 8 hourly.
When there is clinical improvement, change to:

Clindamycin, oral, 450 mg 8 hourly.
4.5 ATOPIC ECZEMA/ DERMATITIS
L30.9
DESCRIPTION
Eczema is an inflammatory skin condition recognised by vesicles, weeping
and crusting in the acute phase; and thickened, scaly skin with increased
skin markings known as lichenification in the chronic phase.
Assessing Severity
1% of body surface is equal to the size of one hand (including the fingers) of
the patient
Mild
» Less than 5% body surface involved.
» No acute changes.
» No significant impact on quality of life.
Moderate
» 5-30% body surface involved.
» Mild dermatitis with acute changes.
» Mild dermatitis with significant impact on quality of life.
Severe
» More than 30% body surface involved.
» Moderate dermatitis with acute changes.
» Moderate dermatitis with significant impact on quality of life.
GENERAL MEASURES
»
»
»
»
»
»
Avoid exposure to trigger or precipitating factors, where applicable.
Avoid irritants such as strong detergents, antiseptics, foam (especially
hot) baths, soaps and rough occlusive clothing (silk is better than cotton,
which is better than nylon, which is better than wool).
Good personal hygiene with once daily washing to remove crusts and
accretions and avoid secondary infection.
Keep fingernails short to minimise trauma from scratching.
Respect patient preference for cream or ointment topical treatment.
Wet wraps may help control eczema and pruritus but should not be
used for infected eczema.
2015
4.5
CHAPTER 4
»
»
DERMATOLOGY
Diet modification has no role in atopic eczema treatment unless double
blind challenge testing proves food sensitivity.
Avoid smoking.
MEDICINE TREATMENT
To relieve skin dryness:

Aqueous cream topical, to wash or bath.

Emulsifying ointment (UE), topical, applied daily to dry areas as a
v
moisturiser.
LoE:III
Creams are preferred to ointments on opening or oozing lesions and in
intertriginous folds.
Moisturising soap, creams and ointments, as described above, should
continue permanently as maintenance, even if the dermatitis is controlled.
Mild eczema

Topical corticosteroids, e.g.:

Hydrocortisone 1%, topical, applied 12 hourly to body and daily to face
until control is achieved.
o Can be used on face and in skin folds.
o Apply sparingly to the face.
o
Use with caution around the eyes.
Moderate and Severe eczema

Potent topical corticosteroids, e.g.:

Betamethasone 0.1%, topical, applied 12 hourly for 7 days to the
affected areas.
vi
o
Apply sparingly to face, neck and flexures.
LoE:III
If non-responsive:
Refer for dermatologist opinion.

Prednisone, oral, for a maximum period of two weeks. Specialist
initiated.
Maintenance therapy
Once eczema is controlled, wean to the lowest potency topical corticosteroid
that maintains remission, applied twice a week.
Apply moisturiser as needed.

Emulsifying ointment (UE), topical, applied daily.
Infected eczema
This is usually due to staphylococcal infection.
LoE: III
Antibiotic therapy

Flucloxacillin, oral, 500 mg 6 hourly for 5 days.
2015
4.6
i
CHAPTER 4
DERMATOLOGY
Severe penicillin allergy:

Clindamycin, oral, 450 mg 8 hourly for 5 days.
For sedation and relief of itch:

Chlorphenamine, oral, 4 mg at night as needed.
Eczema herpeticum.
Therapy should be initiated without delay:

Aciclovir 400 mg, oral, 8 hourly for 7 days.
vii
If patient is unable to swallow due to odynophagia:

Aciclovir, IV, 5 mg/kg/dose, 8 hourly for 7 days.
LoE:III
viii
LoE:III
REFERRAL
Severe, non-responsive or complicated cases or cases with uncertain
diagnosis (e.g. severe infection including disseminated herpes simplex).
4.6 ERYTHEMA MULTIFORME, STEVENS JOHNSON
SYNDROME, TOXIC EPIDERMAL NECROLYSIS
L51.9/L51.1/L51.2
DESCRIPTION
Erythema multiforme
An acute, self-limiting and commonly recurrent inflammatory skin eruption
with variable involvement of the mucous membranes and without systemic
symptoms.
Symmetrically distributed crops of target lesions (dark centre, an inner, pale
ring surrounded by an outer red ring) often involving palms and soles are
characteristic. This condition is usually due to an infection, commonly herpes
simplex or mycoplasma.
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis
(TEN)
Life-threatening acute hypersensitivity reactions with systemic upset,
epidermal necrosis, and mucous membrane involvement. TEN and SJS are
different ends of the same spectrum: in TEN epidermal necrosis involves
>30% of body surface area, while in SJS the involvement is <10%. Nonspecific prodromal symptoms, often mistaken as an upper respiratory tract
infection, may occur before skin lesions are apparent.
Cutaneous lesions may start as a dusky red macular rash, progressing to
confluence with epidermal necrosis and large flaccid blisters which rupture,
leaving large areas of denuded skin. Mucous membrane erosions are
common and multi- organ involvement may be present.
2015
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DERMATOLOGY
This condition is usually due to medication, e.g. sulphonamides, nonnucleoside reverse transcriptase inhibitors (especially nevirapine), antiepileptics (phenytoin, phenobarbitone, carbamazepine, lamotrigine),
allopurinol, laxatives (phenolphtalein).
Complications include:
» Dehydration, electrolyte disturbances and shock,
» hypoalbuminaemia,
» hypo- and more commonly hyperthermia,
» high output cardiac failure,
» secondary infection and sepsis, and
» adhesions and scarring.
Stop all medicines, where safely possible, including complementary,
alternative, and self medication.
GENERAL MEASURES
Principles of management
The foundation of management is supportive, good nursing and the
prevention of dehydration and sepsis.
Management is similar to that of burns.
Stop/substitute all medicines.
Patients usually require care in a high or intensive care unit with dedicated
nursing.
Monitoring
Monitor vital organ function.
Examine daily for infection and swab infected lesions. Do blood cultures if
fever persists or suspicion of infection.
Dressings
Skin hygiene; daily cleansing and bland, non-adherent dressings as needed.
Do not use silver sulfadiazine if SJS/TEN is thought to be due to
cotrimoxazole or other sulphonamide.
Mucous membranes:
Regular supervised oral, genital and eye care to prevent adhesions and
scarring.
Two-hourly mouth washes with bland mouth wash, e.g. glycothymol.
Examine daily for ocular lesions and treat 2-hourly with eye care and
lubricants (methylpropylcellulose drops or ointment) and break down
adhesions.
Treat genitalia 6 hourly with Sitz baths and encourage movement of
opposing eroded surfaces to prevent adhesions.
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4.8
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DERMATOLOGY
Fluids:
Oral rehydration is preferred but intravenous fluid therapy may be required to
treat significant dehydration.
Encourage oral fluids to prevent pharyngeal adhesions.
Provide soft, lukewarm food. Restrict nasogastric feeds to those patients that
are unable to eat, as they may lead to additional trauma with bleeding,
secondary infection and adhesions.
Note: All patients should receive a notification bracelet/necklace on
discharge.
MEDICINE TREATMENT
Corticosteroids
The practice of using systemic corticosteroids is not supported by evidence
and is therefore not recommended.
Antibiotic therapy
Systemic antibiotics may be indicated, depending on results of appropriate
cultures. This should not be administered routinely, nor be given
prophylactically. Organisms identified on skin swabs are not a good indicator
of systemic infection.
Analgesia
Appropriate and adequate analgesia for the pain associated with dressing
changes, given at least half an hour before dressing change. (See section
12.13.3 Analgesia for acute non-surgical pain).
REFFERAL/CONSULTATION
Discuss with a specialist, if considering re-initiation of medicine treatment.
4.7 LEG ULCERS, COMPLICATED
L97
DESCRIPTION
A chronic relapsing disorder of the lower limbs. It has many causes and is
often associated with lipodermatosclerosis (bound-down, fibrosed skin) and
eczema. It is mainly associated with vascular, predominantly venous
insufficiency and immobility. It is also associated with neuropathy and,
occasionally, with infections, neoplasia, trauma or other rare conditions.
GENERAL MEASURES
The aim of management should be to:
» Treat underlying conditions, e.g. heart failure, diabetes mellitus and
venous stasis.
» Limit the extent of damage.
» Encourage rapid healing to minimise scarring and fibrosis.
2015
4.9
CHAPTER 4
»
DERMATOLOGY
Prevent recurrences.
Avoid all topical irritants and allergens, e.g. lanolin, neomycin, bacitracin,
parabens, fusidic acid, clioquinol, antihistamine creams, etc.
If the ulcer is oedema- or stasis-related, rest the leg in an elevated position.
In venous insufficiency, compression (bandages or stockings) is essential to
achieve and maintain healing, provided the arterial supply is normal.
In patients with arterial insufficiency, avoid pressure elevation and
compression bandages or stockings on bony prominences and the toes.
Stress meticulous foot care and avoidance of minor trauma.
Walking and exercises are recommended.
Encourage patients with neuropathy not to walk barefoot, to check their
shoes for foreign objects, examine their feet daily for trauma and to test bath
water before bathing to prevent getting burnt.
Avoid excessive local heat.
Indications for surgical procedures include:
» slough removal
» arterial insufficiency
» surgery for varicose veins
» skin grafting
MEDICINE TREATMENT
Antibiotic therapy
Systemic antibiotics are seldom required for ulcers, and should be
considered only if there is surrounding cellulitis. These infections are
typically polymicrobial and broad-spectrum antibiotics are recommended.

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 7 days.
Local wound care
Topical cleansing
Use bland, non-toxic products to clean the ulcer and surrounding skin.
For clean uninfected wounds:

Sodium chloride 0.9% or sterile water.
Dressed with:

Gauze moistened with sodium chloride 0.9%.
ix
For exudative, infected wounds:

Povidone-iodine 5% cream, topical apply daily.
LoE:I
4.8 PSORIASIS
L40.9
DESCRIPTION
This is an inflammatory condition of the skin and joints of unknown aetiology.
Scaly red, papules and plaques over extensor surfaces and on the scalp are
2015
4.10
CHAPTER 4
DERMATOLOGY
common. The nails and skin folds are often involved. In exceptional cases, it
is localised to palms and soles and pustular skin lesions are seen, especially
following rapid treatment withdrawal, e.g. steroids or systemic agents.
GENERAL MEASURES
Counselling regarding precipitating factors and chronicity.
Encourage sun exposure as tolerated.
MEDICINE TREATMENT
Note: Systemic steroids should be avoided.
Local plaques
For maintenance:

Coal tar 6% ointment, topical, apply at night.
o Avoid use on the face, flexures and genitalia.
For flares:

Betamethasone 0.1%, topical, apply 12 hourly.
o Decrease according to severity, reduce to
hydrocortisone 1%, then stop.
Scalp psoriasis
For maintenance:

Wash with coal tar containing shampoo.
OR
Coal tar 1% ointment, topical, apply at night, under
occlusion and wash out the next morning.
x
LoE:III
xi
LoE:III
For flares:

Betamethasone 0.1% lotion, topical, apply once daily.
REFERRAL
»
»
Indequate response to topical treatment.
Severe disease, especially if joint involvement.
4.9 URTICARIA
L50.9
DESCRIPTION
A transient itchy inflammatory skin and mucosal condition recognised by a
wheal and flare reaction. There are many causes. In most chronic cases the
precipitant for the urticaria is never found. Lesions due to insect bites are
often grouped, show a central bite mark, are on exposed areas of the
body,and are often associated excoriations, vesicles, pigmentary changes
and secondary infection.
2015
4.11
CHAPTER 4
DERMATOLOGY
GENERAL MEASURES
Limit exposure to triggers such as non-immune mast cell degranulators,
which aggravate and prolong urticaria, e.g. opioids (such as codeine),
NSAIDs, salicylates, alcohol, etc.
MEDICINE TREATMENT
Antihistamines
Regular use is recommended until the urticaria is quiescent.
For chronic urticaria less sedating antihistamines are preferable:

Cetirizine, oral, 10 mg daily.
Avoid oral corticosteroids.
REFERRAL
All patients with urticarial lesions where the individual lesions remain for
longer than 48 hours to a specialist to exclude urticarial vasculitis.
4.9.1 PAPULAR URTICARIA
L50.9
DESCRIPTION
Papular urticaria is a hypersensitivity disorder to insect bites, resulting in
recurrent and sometimes chronic itchy papules on exposed areas of the
body.
Initial lesion is a red papule, which may blister, become excoriated, and then
heal with hyperpigmentation.
Usually occur in crops over several months.
Chronic, severe, persistent reactions may be seen in immunocompromised
patients, e.g. HIV infection, immunosuppressive therapy and malnutrition.
GENERAL MEASURES
Reduce exposure to insects by treating pets, using mosquito nets and
fumigating household regularly.
Use of insect repellents may be helpful.
Examine carefully for burrows to rule out scabies.
MEDICINE TREATMENT
New inflamed lesions:

Betamethasone 0.1%, topical apply daily for 5 days.
For relief of itch and sedation:

Chlorphenamine, oral, 4 mg at night as needed in severe cases.
REFERRAL
Non-responsive and chronic cases.
2015
4.12
CHAPTER 4
DERMATOLOGY
4.10 FUNGAL INFECTIONS
B35
DESCRIPTION
The skin may be infected by fungi and the clinical presentation varies with
organism, body site infected and the body’s response to the infection.
GENERAL MEASURES
Manage predisposing factors, i.e. occlusion, maceration and underlying
conditions such as diabetes mellitus, eczema, immunocompromising
conditions, etc.
Advise patient regarding spread of infection and exposure in communal,
shared facilities (dermatophytes).
MEDICINE TREATMENT
Yeast and dermatophytes (Fungal infection of the skin):

Imidazole, e.g.:

Clotrimazole 1%, topical, apply 8 hourly until clear of disease (i.e. for at
least 2 weeks after the lesions have cleared).
Pityriasis versicolor:

Selenium sulphide 2.5% suspension, applied once weekly to all affected
areas.
o Allow to dry and leave overnight before rinsing off.
o Repeat for 3 weeks.
Systemic antifungal therapy
Topical treatment is generally ineffective for dermatophyte hair and nail
infections.
Systemic therapy may be indicated for immunocompromised individuals with
extensive skin infection
Recurrent infections are not uncommon if repeat exposure is not prevented.

Fluconazole, oral, 200 mg weekly for 6 weeks.
o For onychomycosis, 200 mg weekly for 6 months.
xii
LoE:I
REFERRAL
»
»
Non-responsive infections.
Systemic infections.
2015
4.13
CHAPTER 4
DERMATOLOGY
4.11 VIRAL INFECTIONS
4.11.1 VIRAL WARTS/ANOGENITAL WARTS
B07/A63.0
DESCRIPTION
Superficial muco-cutaneous infection caused by the human papilloma virus.
GENERAL MEASURES
Patients with anogenital warts are at an increased risk of other STIs.
Anogaenital warts:
» Pap smear should be done in women.
» Screen for other STIs.
MEDICINE TREATMENT
Cutaneous warts
Treatment seldom indicated.
Anogenital warts

Podophyllin 20% in Tinct. Benz. Co., topical.
o Apply at weekly intervals to lesions by a health care professional
until lesions disappear.
o Apply petroleum jelly to surrounding skin and mucous membrane
for protection.
o Wash the solution off after 4 hours.
Podophyllin is a cytotoxic agent.
Avoid systemic absorption.
Contraindicated in pregnancy.
REFERRAL
Extensive or recurrent anogenital warts.
4.11.2 SHINGLES (HERPES ZOSTER)
See section 9.11: Zoster (shingles).
References:
i
Benzoyl peroxide 5% gel: SAMF, 2014.
ii
Doxycycline, oral: SAMF, 2014.
iii
Cyproterone acetate 2 mg plus Ethinyl Estradiol 35 µg, oral: Arowojolu AO, Gallo MF, Lopez LM, Grimes DA.
Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012 Jul 11;7:CD004425.
http://www.ncbi.nlm.nih.gov/pubmed/22786490
Cyproterone acetate 2 mg plus Ethinyl Estradiol 35 µg, oral: SAMF, 2014.
iv
Azithromycin,oral: Contract circular HP02-2015AI. http://www.health.gov.za/
v
Aqueous cream and emollients: Tsang M, Guy RH. Effect of aqueous cream BP on human stratum corneum in vivo.
Br J Dermatol2010; 163:954–8.http://www.ncbi.nlm.nih.gov/pubmed/20649794
Aqueous cream and emollients: Mohammed D, Matts PJ, Hadgraft J, Lane ME. Influence of aqueous cream BP on
corneocyte size, maturity, skin protease activity, protein content and transepidermal water loss. Br J Dermatol 2011;
2015
4.14
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DERMATOLOGY
164:1304–10.http://www.ncbi.nlm.nih.gov/pubmed/21443526
Aqueous cream and emollients: Danby S, Cork MJ. A new understanding of atopic dermatitis: the role of epidermal
barrier dysfunction and subclinical inflammation. J ClinDermatol 2010; 1:33–46.
Aqueous cream and emollients: Hoare C, Li Wan Po A,Williams H. Systematic review of treatments of atopic
eczema. Health Technol Assess 2000;4(37).http://www.ncbi.nlm.nih.gov/pubmed/11134919
Aqueous cream and emollients: Lewis-Jones S, Cork MJ, Clark C et al. Atopic Eczema in Children – Guideline
Consultation: A Systematic Review of the Treatments for Atopic Eczema and Guideline for its Management. London:
National Institute for Clinical Excellence (NICE), 2007.https://www.nice.org.uk/guidance/cg57
vi
Betamethasone 0.1%, topical: Contract circular HP08-2014SSP. http://www.health.gov.za/
vii
Aciclovir: Workowski KA, Bolan GA: Centers for Disease Control and Prevention (CDC). Sexually transmitted
diseases treatment guidelines, 2015.MMWR Recomm Rep. 2015;64; RR-3):1-140.
http://www.cdc.gov/std/tg2015/tg-2015-print.pdf
viii
Aciclovir: Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence-based review.
Arch Intern Med. 2008 Jun 9;168(11):1137-44. http://www.ncbi.nlm.nih.gov/pubmed/18541820
ix
Dressing: Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA. Dressings for healing venous leg ulcers.
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD001103. Review. Update in: Cochrane Database Syst Rev.
2014;5:CD001103. http://www.ncbi.nlm.nih.gov/pubmed/16855958
ix
Betamethasone 0.1%, topical: Contract circular HP08-2014SSP. http://www.health.gov.za/
x
Betamethasone 0.1%, topical: Contract circular HP08-2014SSP. http://www.health.gov.za/
xi
Coal tar shampoo: Contract circular HP08-2014SSP. http://www.health.gov.za/
xii
Fluconazole, oral: Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents
for the treatment of onychomycosis. Br J Dermatol. 2004 Mar;150(3):537-44.
http://www.ncbi.nlm.nih.gov/pubmed/15030339
Fluconazole: Contract circular HP02-2015AI. http://www.health.gov.za/
Fluconazole: Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silny W. A comparison of the
efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea
pedis, and cutaneous candidosis. Int J Dermatol. 1998 Sep;37(9):703-5.
http://www.ncbi.nlm.nih.gov/pubmed/9762826
Fluconazole: Faergemann J, Mörk NJ, Haglund A, Odegård T. A multicentre (double-blind)
comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea
corporis and tinea cruris. Br J Dermatol. 1997 Apr;136(4):575-7. http://www.ncbi.nlm.nih.gov/pubmed/91559
2015
4.15
CHAPTER 5
GYNAECOLOGY
5.1 DYSMENORRHOEA
N94.6
DESCRIPTION
Lower abdominal pain that starts with the onset of menstruation, and subsides after
menses have ended. It may be primary or secondary.
Primary dysmenorrhoea is menstrual pain without organic disease
Secondary dysmenorrhoea is associated with identifiable disease, e.g. chronic
pelvic infection, fibroids, endometriosis, adenomyosis and use of intrauterine
contraceptive device.
GENERAL MEASURES
For secondary dysmenorrhoea, investigate and treat the underlying condition.
MEDICINE treatment
Symptomatic relief:

Ibuprofen, oral, 400 mg 8 hourly with meals.
OR

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum
of 4 doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
For dysmenorrhoea caused by endometriosis:
ADD

A combined oral contraceptive and review after 3 months.
OR
Medroxyprogesterone acetate (long-acting), IM, 150 mg, 12
weekly.
o Review after 3 months.
i
LoE:III
LoE:III
ii
LoE:I
iii
LoE:II
REFERRAL
If there is uncertainty about the diagnosis.
Young women with pain not responding to conventional treatment.
Older (> 40 years of age) women with persistent pain.
5.2 UTERINE BLEEDING, ABNORMAL
N91.0–N93.9
GENERAL MEASURES
All women over 45 years of age should have a transvaginal ultrasound and
endometrial sampling.
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5.1
CHAPTER 5
GYNAECOLOGY
Actively exclude organic causes, e.g. fibroids, for abnormal uterine bleeding.
MEDICINE treatment
Dysfunctional uterine bleeding implies that no organic cause is present.
Arrest of acute haemorrhage
Progestin, e.g.:

Norethisterone, oral, 5 mg 4 hourly until bleeding stops up to a
maximum 48 hours.
OR
Tranexamic acid, oral, 1g 6 hourly on days 1–4 of the cycle.
iv
LoE:III
v
After bleeding has stopped, continue with:

Combined oral contraceptive, oral, 1 tablet 8 hourly for 7 days.
o Follow with 1 tablet once daily for 3 months.
LoE:I
For restoring cyclicity
For women in the reproductive years:

Combined oral contraceptive, oral, 1 tablet daily for 6 months.
OR
As alternative to combined oral contraceptives:
Progestin only:

Medroxyprogesterone acetate, oral, 30 mg daily from day 5 to
day 26 of the cycle.
o Use for 3–6 cycles.
OR

Norethisterone, oral, 15 mg daily from day 5 to day 26 of the cycle.
o Use for 3–6 cycles.
OR

NSAID, oral: e.g.

Ibuprofen, oral, 400 mg 8 hourly with meals.
st
o Begin trial of NSAID starting on 1 day of menses until
menses cease.
OR

Tranexamic acid, oral, 1 g 6 hourly on days 1–4 of the cycle.
vi
LoE:III
vii
LoE:I
viii
LoE:I
For perimenopausal women, hormone therapy (HT):

Conjugated oestrogens, oral, 0.625 mg daily for 21 days with the addition of
medroxyprogesterone acetate, oral 10 mg daily from day 11 to day 21.
o Day 22– 28 no treatment.
o Use for 3–6 cycles.
ADD
For dysmenorrhoea and abnormal bleeding:

Ibuprofen, oral, 400 mg 8 hourly for 2–3 days with meals, depending on
severity of pain.
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5.2
CHAPTER 5
GYNAECOLOGY
REFERRAL
Refer for surgical procedures as dictated by the diagnosis.
5.3 PELVIC INFLAMMATORY DISEASE (PID)
N73.9
DESCRIPTION
PID includes salpingitis with or without oöphoritis and, as precise clinical
localisation is often difficult, denotes the spectrum of conditions resulting from
infection of the upper genital tract.
Sequelae include:
» recurrent infections if inadequately treated,
» infertility,
» increased probability of ectopic pregnancy, and
» chronic pelvic pain.
Stage
Stage I
»
Stage II
Stage III
»
»
»
»
»
»
Stage IV
Manifestations
cervical motion tenderness and/or uterine
tenderness and/or adnexal tenderness
as stage I, plus pelvic peritonitis
as stage II, plus
tubo-ovarian complex or abscess
generalised peritonitis
ruptured tubo-ovarian complex
septicaemia
GENERAL MEASURES
Hospitalise all patients with stage II–IV PID for parenteral antibiotic therapy.
Frequent monitoring of general abdominal and pelvic signs is essential.
Admission for parenteral therapy, observation, further investigation and/or possible
surgical intervention should also be considered in the following situations:
» a surgical emergency cannot be excluded
» lack of response to oral therapy
» clinically severe disease
» presence of a tubo-ovarian abscess
» intolerance to oral therapy
» pregnancy
Further Investigation
All sexually active patients should be offered:
» a pregnancy test
» screening for sexually transmitted infections including HIV
Perform a pregnancy test, as an ectopic pregnancy forms part of the differential
diagnosis.
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5.3
CHAPTER 5
GYNAECOLOGY
Note: Remove IUDs.
In stage III, surgery is indicated if:
» the diagnosis is uncertain,
» there is no adequate response after 48 hours of appropriate therapy,
» the patient deteriorates on treatment, or
» there is a large or symptomatic pelvic mass after 4–6 weeks.
MEDICINE TREATMENT
Stage I

Azithromycin, oral, 1 g as a single dose
ix
AND
LoE:II

Ceftriaxone, IM, 250 mg as a single dose.
o Dissolve ceftriaxone, IM, 250 mg in 0.9 mL lidocaine 1% without
adrenaline (epinephrine).
x
AND
LoE:III

Metronidazole, oral, 400 mg 12 hourly for 7 days.
xi
LoE:III
Severe penicillin allergy:

Azithromycin, oral, 2 g as a single dose
xii
AND
LoE:I

Metronidazole, oral, 400 mg 12 hourly for 7 days.
Stage II–IV

Ceftriaxone, IV, 1 g daily
AND

Metronidazole, IV, 500 mg 8 hourly.
Continue intravenous therapy until there is definite clinical improvement (within 2448 hours). Thereafter, change to:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly to complete 10 days
therapy.
xiii
AND
LoE:III
To treat chlamydia:

Azithromycin, oral, 1 g, as a single dose.
Note: The addition of metronidazole to amoxicillin/clavulanic acid is unnecessary as
amoxicillin/clavulanic acid has adequate anaerobic cover.
Severe penicillin allergy:
 Clindamycin, IV, 600 mg 8 hourly.
AND
 Gentamicin, IV, 6 mg/kg daily.
Continue intravenous therapy until there is definite clinical improvement (within 2448 hours). Thereafter, change to:
 Clindamycin, oral, 450mg 8 hourly.
AND
2015
5.4
CHAPTER 5
GYNAECOLOGY
 Ciprofloxacin, oral, 500 mg 12 hourly to complete 10 days’ therapy.
AND
To treat chlamydia:

Azithromycin, oral, 1 g, as a single dose.
xiv
LoE:III
Note: The addition of metronidazole to clindamycin is unnecessary as clindamycin
has adequate anaerobic cover.
REFERRAL
Stages III and IV should be managed in consultation with a gynaecologist.
5.4 ENDOMETRIOSIS
N80
DESCRIPTION
The presence and proliferation of endometrial tissue outside the uterine cavity,
usually within the pelvis. It may manifest as dysmenorrhoea, dyspareunia and
chronic pelvic pain. Diagnosis is made by laparoscopy.
MEDICINE TREATMENT
For pain:

NSAID, oral: e.g.

Ibuprofen, oral, 400 mg 8 hourly with meals.
LoE:III
AND


Combined oral contraceptives for 6 months.
OR
Medroxyprogesterone acetate, oral, 30 mg daily for at least 3 months.
Note: The recurrence of symptoms is common following cessation of treatment.
REFERRAL
»
»
Women with infertility.
No response to treatment after 3 months.
5.5 AMENORRHOEA
N91.0/N91.1
DESCRIPTION
Primary amenorrhoea: no menstruation by 16 years of age in the presence of
secondary sexual characteristics.
Secondary amenorrhoea: amenorrhoea for at least 3 months in women with
previous normal menses.
2015
5.5
CHAPTER 5
GYNAECOLOGY
Investigations
» Body mass index.
» Urine pregnancy test.
» Pelvic ultrasound.
» Serum for TSH, FSH, LH, prolactin.
 FSH > 15 units/L in a woman < 40 years of age suggests premature
ovarian failure.
 LH/FSH ratio of > 2:1 suggests polycystic ovarian syndrome.
MEDICINE TREATMENT
For treatment of hyperprolactinaemia, hypo- or hyperthyroidism, see Chapter 8:
Endocrine System.
Progestin challenge test:
If no cause for secondary amenorrhoea is found:

Medroxyprogesterone acetate, oral, 10 mg daily for 10 days.
o Anticipate a withdrawal bleed 5–7 days following conclusion of treatment.
REFERRAL
»
»
»
All cases of primary amenorrhoea.
Secondary amenorrhoea not responding to medroxyprogesterone acetate.
Polycystic ovarian syndrome and premature ovarian failure, for further
evaluation.
5.6 HIRSUTISM AND VIRILISATION
L68.0/E25
DESCRIPTION
Hirsutism refers to terminal hair growth in amounts that are socially undesirable,
typically following a male pattern of distribution. Virilisation refers to the development
of male secondary sexual characteristics in a woman.
Refer to a tertiary hospital for investigation and management.
REFERRAL
All cases.
5.7 INFERTILITY
N97.9
DESCRIPTION
Inability to conceive after a year of regular sexual intercourse without contraception.
GENERAL MEASURES
Counselling.
2015
5.6
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GYNAECOLOGY
Lifestyle modification, e.g. weight optimisation, smoking cessation and regular
sexual intercourse.
Investigations
» Partner semen analysis.
» Prolactin level.
» Mid-luteal (day 21) progesterone assay: > 30 nmol/L suggests adequate
ovulation.
» Laparoscopy and/or hysterosalpingography (Specialist supervision).
MEDICINE TREATMENT
Treat the underlying disease.
For induction of ovulation:

Clomifene, oral, 50 mg daily on days 5–9 of the cycle. Specialist only.
o Monitor the progress of ovulation.
For hyperprolactinaemia after further investigation:
See section 8.15.1: Prolactinoma.
5.8 MISCARRIAGE
O00–O08
Both Manual Vacuum Aspiration (MVA) and medical evacuation are equally
effective for miscarriage. However, in the follow settings, MVA is preferred:
» septic miscarriage
» anaemia
» haemodynamic instability
» second trimester miscarriage
5.8.1 SILENT MISCARRIAGE OR EARLY FETAL DEATH
O02.0
GENERAL MEASURES
Counselling.
Evacuation of the uterus.
MEDICINE TREATMENT
Before MVA, to ripen the cervix:

Misoprostol, PV, 400 mcg as a single dose.
Medical evacuation:
 Misoprostol, oral/PV, 600 mcg as a single dose.
o
Repeat after 24 hours if necessary.
2015
5.7
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GYNAECOLOGY
5.8.2 INCOMPLETE MISCARRIAGE IN THE FIRST TRIMESTER
O02.1
GENERAL MEASURES
Counselling.
Evacuation of the uterus after ripening the cervix.
MEDICINE TREATMENT
Before MVA, to ripen the cervix:

Misoprostol, oral/PV, 400 mcg as a single dose.
Medical evacuation:

Misoprostol, oral/PV, 600 mcg as a single dose.
o Repeat after 24 hours if necessary.
5.8.3 MIDTRIMESTER MISCARRIAGE (FROM 13–22 WEEKS
GESTATION)
O03.4
GENERAL MEASURES
Counselling.
Evacuation of the uterus after the fetus has been expelled.
MEDICINE TREATMENT
If no cervical dilatation:

Misoprostol, PV, 400 mcg immediately.
Follow with:

Misoprostol, oral, 400 mcg every 4 hours until expulsion of the products of
conception.
o
Duration of treatment must not exceed 24 hours.
Warning
Misoprostol can cause uterine rupture in women with previous
Caesarean sections and those of high parity.
In these women use 200 mcg of misoprostol or alternative methods
such as extra-amniotic saline infusion without misoprostol.
If cervical dilatation already present:

Oxytocin, IV.
o Dilute 20 units in 1 L sodium chloride 0.9%, i.e. 20 milliunits/mL solution,
and infuse at 125 mL/hour.
o Reduce rate if strong contractions are experienced.
Note: Check serum sodium if used for more than 24 hours because of the
danger of dilutional hyponatraemia.
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5.8
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GYNAECOLOGY
For analgesia:

Morphine, IV, to a maximum dose of 10 mg (See Appendix II, for individual
dosing and monitoring for response and toxicity).
If Rh-negative:

Anti-D immunoglobulin, IM, 100 mcg as a single dose.
REFERRAL
»
»
»
»
»
Uterine abnormalities.
Recurrent miscarriages (3 consecutive spontaneous miscarriages).
Suspected cervical weakness: mid-trimester miscarriage(s) with minimal pain
and bleeding.
Diabetes mellitus.
Parental genetic defects and SLE or other causes of autoimmune disease.
5.8.4 SEPTIC MISCARRIAGE
O03.87
GENERAL MEASURES
Counselling.
Urgent evacuation of uterus (under general anaesthesia and not a MVA) and
surgical management of complications.
MEDICINE TREATMENT

Oxytocin, IV.
o Dilute 20 units in 1 L sodium chloride 0.9%, i.e. 20 milliunits/mL solution
administered at a rate of 125 mL/hour.
o Reduce rate if strong contractions are experienced.
Antibiotic therapy

Amoxicillin/clavulanic acid, IV, 1.2 g, 8 hourly.
Change to oral treatment after clinical improvement:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 7–10 days.
Note: The addition of metronidazole to amoxicillin/clavulanic acid is unnecessary as
amoxicillin/clavulanic acid has adequate anaerobic cover.
LoE:III
Severe penicillin allergy:

Clindamycin, IV, 600 mg 8 hourly.
AND

Gentamicin, IV, 6 mg/kg daily.
Change to oral treatment after improvement:

Clindamycin, oral, 450 mg 8 hourly for 5 days.
AND

Ciprofloxacin, oral, 500 mg 12 hourly.
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5.9
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GYNAECOLOGY
Note: The addition of metronidazole to clindamycin is unnecessary as clindamycin
has adequate anaerobic cover.
If patient has severe sepsis, consider urgent hysterectomy.
REFERRAL
»
»
Evidence of trauma.
No response to treatment within 48 hours.
5.8.5 TROPHOBLASTIC NEOPLASIA (‘HYDATIDIFORM MOLE’)
O01.9
Misoprostol is not indicated in this condition because of risk of dissemination.
Send products of conception for histology.
REFERRAL
All patients.
5.9 TERMINATION OF PREGNANCY (TOP)
O04
Early ultrasound examination is more accurate than last normal menstrual period
at determining gestational age, and also of value in identifying ectopic pregnancy,
molar pregnancy or twins.
Summary of Choice of Termination of Pregnancy Act
Women eligibility
st
1 trimester (< 13 weeks): on request.
Second trimester (13 to 20 weeks): If doctor is satisfied that pregnancy was from
rape or incest, or there is risk of fetal abnormality or risk to mother’s physical or
mental health or social or economic circumstances.
More than 20 weeks: Doctor and second doctor or registered midwife are satisfied
that there is danger to the mothers’ life, a lethal or severe fetal malformation or
fetal death.
Venue
An accredited facility with staff trained in performing TOP, designated by the
Member of Executive Council at provincial level.
Practitioner
st
1 trimester (< 13 weeks): doctor, midwife or registered nurse with appropriate
training.
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5.10
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GYNAECOLOGY
Second trimester (13 to 20 weeks), onwards: doctor responsible for decision and
prescription of medication. Registered nurse/midwife may administer medication
according to prescription.
Pre and post termination counselling is essential.
Consent of spouse/partner is not necessary.
Consent for TOP and related procedures e.g. laparotomy may be given by minors.
Minors are encouraged to consult parents or others, but consent is not mandatory.
5.9.1 GESTATION, 1ST TRIMESTER (< 13 WEEKS)
O04
GENERAL MEASURES
Counselling.
Outpatient procedure by nursing staff with specific training.
Discuss TOP options with patient: Manual vacuum aspiration of the uterus or
xv
medical TOP.
LoE:III
MEDICINE TREATMENT
Manual vacuum aspiration:
Misoprostol, PV, 400 mcg 3 hours before routine vacuum aspiration of the uterus.
Routine analgesia for vacuum aspiration:

Pethidine, IM, 1 mg/kg 30 minutes before aspiration procedure, to a
maximum of 100 mg.
xvi
LoE:III
OR

Morphine, IM, 0.1 mg/kg 30 minutes before aspiration procedure, to a
xvii
maximum of 10 mg (Doctor initiated).
LoE:III
Do not give intravenous benzodiazepines and parenteral opioid analgesics
concurrently.
Conscious sedation - see chapter 23: Sedation.
Alternatively, consider paracervical block.
Oral analgesia as required for 48 hours:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
AND

Ibuprofen, oral, 400 mg 8 hourly with meals.
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5.11
CHAPTER 5
GYNAECOLOGY
Medical TOP:
An alternative to MVA:

Mifepristone, oral, 200 mg, immediately as a single dose.
LoE:III
Followed 24–48 hours later by:

Misoprostol, PV, 800 mcg.
o If expulsion has not occurred 4 hours after misoprostol administration, a
second dose of misoprostol 400 mcg oral/PV may be given.
o Review with ultrasound on day 7.
Note: Bleeding may persist for up to 1 week.
After administration of mifepristone, start:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
ADD
After expulsion is complete:

Ibuprofen, oral, 400 mg 8 hourly with meals.
5.9.2 GESTATION, SECOND TRIMESTER (13 TO 20 WEEKS)
Inpatient care in facilities with 24-hour service and facilities for general anaesthesia.
GENERAL MEASURES
Manual vacuum aspiration of the uterus, if expulsion of products of conception is not
complete.
MEDICINE TREATMENT
The dose of misoprostol, PV, decreases with increasing gestational age because of
the risk of uterine rupture.

Misoprostol, PV, 3 hourly to a maximum of 5 doses
+6
o 13 to 16 weeks: 400 mcg, PV.
o 17 to 20 weeks: 200 mcg, PV.
xviii
LoE:III
Mifepristone, oral, 200 mg, oral, immediately as a single dose.
xix
LoE:III
Followed 24–48 hours later by:

Misoprostol, PV, 400–800 mcg as a single dose.
o Then, misoprostol, PV, 400 mcg 3 hourly for 5 doses at gestation 13–
+6
16 weeks.
OR
o Misoprostol, PV, 200 mcg 3 hourly for 5 doses at gestation 17–20 weeks.
2015
5.12
CHAPTER 5
GYNAECOLOGY
If no response after 24 hours, consider adding mechanical cervical ripening in
consultation with a specialist.
Pass a Foley catheter with 30 mL bulb through cervix with sterile technique. Inflate
bulb with 50 mL water or sodium chloride 0.9%.
Tape catheter to thigh with light traction on catheter.
Attach sodium chloride 0.9% 1 L with giving set to catheter and infuse at 50 mL/
hour through catheter into uterus.
Warning
Misoprostol can cause uterine rupture in women with previous Caesarean
sections and those of high parity. In these women use 200 mcg of
misoprostol or alternative methods such as extra-amniotic saline infusion
without misoprostol.
Analgesia

Pethidine, IM, 1 mg/kg 4 hourly as needed, to a maximum of 100 mg.
OR

Morphine, IM, 0.1 mg/kg 4 hourly as needed, to a maximum of 10 mg.
If Rh-negative:

Anti-D immunoglobulin, IM, 100 mcg as a single dose.
REFERRAL
»
»
»
Complicating medical conditions, e.g. cardiac failure, etc.
Failed procedure.
Ectopic pregnancy.
5.10 SEXUAL ASSAULT
Y05
INVESTIGATIONS
Urine pregnancy test
Blood for:
» Syphilis serology,
» HIV, and
» Hepatitis B if no history of previous Hep B immunisation.
GENERAL MEASURES
Trauma counselling and completion of J88 forms.
Examination under anaesthesia may be required for adequate forensic sample
collection, or repair of genital tract trauma.
2015
5.13
CHAPTER 5
GYNAECOLOGY
MEDICINE TREATMENT
Emergency contraception:

Levonorgestrel 1.5 mg, oral, preferably within 24 hours of event.
Note: Emergency contraception can be given up to 5 days following an episode of
unprotected intercourse.
xx
OR
LoE:I

Copper IUD, e.g.:

Cu T 380A, within 5 days of unprotected intercourse.
xxi
LoE:I
STI prophylaxis

Ceftriaxone, IM, 250 mg as a single dose.
o For ceftriaxone IM injection: Dissolve ceftriaxone 250 mg in 0.9 mL
lidocaine 1% without epinephrine (adrenaline).
AND
xxii
LoE:III

Azithromycin, oral, 1 g, as a single dose.
AND

Metronidazole, oral, 2 g immediately as a single dose.
HIV post-exposure prophylaxis (PEP)
See section10.4.2: Non occupational post exposure prophylaxis, sexual assault
and inadvertent exposure.
5.11 URINARY INCONTINENCE
N81.9
See section: 7.3.6 Overactive bladder.
5.12 MENOPAUSE AND PERIMENOPAUSAL SYNDROME
N95.9
GENERAL MEASURES
Counselling.
Stop smoking.
Maintain a balanced diet.
Regular exercise
MEDICINE treatment
Hormone replacement therapy (HT)
This is not indicated in all postmenopausal women. Women with significant
menopausal symptoms and those with osteoporosis risk factors will benefit most.
The benefits of HT need to be weighed against the potential harm (e.g. breast
cancer, venous thrombo-embolism).
Note: Contraindications to HT: Current, past or suspected breast cancer.
»
»
2015
Known or suspected oestrogen-dependent malignant tumours.
Undiagnosed genital bleeding.
5.14
CHAPTER 5
»
»
»
»
»
»
GYNAECOLOGY
Untreated endometrial hyperplasia.
Previous idiopathic or current venous thrombo-embolism.
Known arterial CHD.
Active liver disease.
Porphyria.
Thrombophilia.
Intact uterus (no hysterectomy)
HT can be offered as sequentially opposed or continuous combined preparations.
Continuous combined preparations have the advantage of less breakthrough
bleeding, but should only be commenced once the woman has been stable on
sequentially opposed therapy for a year. Treatment should be planned for 5 years
but reviewed annually.
Sequentially opposed therapy:

Conjugated equine estrogens, oral, 0.3–0.625 mg daily for 21 days.
o Add medroxyprogesterone acetate, oral, 5–10 mg daily from day 11–21.
o Followed by no therapy from day 22–28.
OR

Estradiol valerate, oral, 1–2 mg daily for 11 days.
o Add medroxyprogesterone acetate, oral, 10 mg daily from day 11–21.
o Followed by no therapy from day 22–28.
Equivalent doses to medroxyprogesterone acetate:

Norethisterone acetate, oral, 1 mg daily from day 11–21.

Cyproterone acetate, oral, 1 mg daily from day 11–21.
Continuous combined therapy, e.g.:

Conjugated equine estrogens, oral, 0.3–0.625 mg plus medroxyprogesterone
acetate, oral, 2.5–5mg daily.
OR

Estradiol valerate, oral, 0.5–1 mg plus norethisterone acetate, oral, 0.5–1 mg
daily.
Note:
» Start at the lowest possible dose to alleviate symptoms. The need to continue
HT should be reviewed annually. Abnormal vaginal bleeding requires specialist
consultation/referral.
» Any unexpected vaginal bleeding is an indication for excluding endometrial
carcinoma. The use of transvaginal ultrasound to measure endometrial
thickness plus the taking of an endometrial biopsy are recommended.
2015
5.15
CHAPTER 5
GYNAECOLOGY
Uterus absent (post hysterectomy)
HT is given as estrogen only:

Estradiol valerate, oral, 1–2 mg daily.
OR

Conjugated equine estrogens, oral, 0.3 mg daily or 0.625 mg on alternative
days up to a maximum of 1.25 mg daily.
REFERRAL
»
»
»
»
Premature menopause, i.e. < 40 years of age.
Severe osteoporosis.
Management difficulties, e.g. where a contra-indication to oestrogen
replacement therapy exists.
Post-menopausal bleeding.
References:
i
Ibuprofen (ceiling effect): Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between
blood levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7..
http://www.ncbi.nlm.nih.gov/pubmed/3522030
ii
Combined oral contraceptive (dysmenorrhea caused by endometriosis): Wong CL, Farquhar C, Roberts H, Proctor M.
Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD002120.
http://www.ncbi.nlm.nih.gov/pubmed/19821293
Combined oral contraceptive (dysmenorrhea caused by endometriosis): American College of Obstetricians and
Gynecologists. ACOG practice bulletin no. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol.
2010;115(1):206-218. http://www.ncbi.nlm.nih.gov/pubmed/20027071
Combined oral (dysmenorrhea caused by endometriosis): Davis L, Kennedy SS, Moore J, Prentice A. Modern
combined oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev. 2007 Jul
18;(3):CD001019. http://www.ncbi.nlm.nih.gov/pubmed/17636650
iii Medroxyprogesterone acetate, IM: Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcutaneous injection of
depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain.
Fertil Steril. 2006 Feb;85(2):314-25. http://www.ncbi.nlm.nih.gov/pubmed/16595206
Medroxyprogesterone acetate, IM: Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot
medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod
2006; 21:248–256. http://www.ncbi.nlm.nih.gov/pubmed/16176939
iv
Progestin, oral (therapeutic class – arrest of acute haemmhorhage): James AH, Kouides PA, Abdul-Kadir R, Dietrich
JE, Edlund M, Federici AB, Halimeh S, Kamphuisen PW, Lee CA, Martínez-Perez O, McLintock C, Peyvandi F, Philipp C,
Wilkinson J, Winikoff R. Evaluation and management of acute menorrhagia in women with and without underlying bleeding
disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):124-34.
http://www.ncbi.nlm.nih.gov/pubmed/21632169
v
Tranexamic acid: Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database
Syst Rev. 2000;(4):CD000249. http://www.ncbi.nlm.nih.gov/pubmed/11034679
Tranexamic acid: Leminen H, Hurskainen R. Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy
and safety. Int J Womens Health. 2012;4:413-21. http://www.ncbi.nlm.nih.gov/pubmed/22956886
Tranexamic acid: Sundström A, Seaman H, Kieler H, Alfredsson L. The risk of venous thromboembolism associated
with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice
Research Database. BJOG. 2009 Jan;116(1):91-7. http://www.ncbi.nlm.nih.gov/pubmed/19016686
vi
Progestin,oral (therapeutic class – restoring cyclicity): Singh S, Best C, Dunn S, Leyland N, Wolfman WL; Clinical
Practice – Gynaecology Committee, Leyland N, Wolfman W, Allaire C, Awadalla A, Best C, Dunn S, Heywood M, Lemyre
M, Marcoux V, Menard C, Potestio F, Rittenberg D, Singh S; Society of Obstetricians and Gynaecologists of Canada.
Abnormal uterine bleeding in pre-menopausal women. J Obstet Gynaecol Can. 2013 May;35(5):473-9.
http://www.ncbi.nlm.nih.gov/pubmed/23756279
Progestin,oral (therapeutic class – restoring cyclicity): Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP.
Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2012 Jan
1;85(1):35-43. http://www.ncbi.nlm.nih.gov/pubmed/22230306
vii
NSAID: Serrant-Green L. Review: non-steroidal anti-inflammatory drugs reduce menstrual pain and heavy bleeding
associated with an intrauterine device. Evid Based Nurs. 2007 Apr;10(2):48.
http://www.ncbi.nlm.nih.gov/pubmed/17384100
viii
Tranexamic acid, oral: Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane
Database Syst Rev. 2000;(4):CD000249. http://www.ncbi.nlm.nih.gov/pubmed/11034679
Tranexamic acid, oral: Callender ST, Warner GT, Cope E. Treatment of menorrhagia with tranexamic acid. A double-
2015
5.16
CHAPTER 5
GYNAECOLOGY
blind trial. Br Med J. 1970 Oct 24;4(5729):214-6. http://www.ncbi.nlm.nih.gov/pubmed/4919554
ix
Azithromycin: Savaris RF, Teixeira LM, Torres TG, Edelweiss MI, Moncada J, Schachter J. Comparing ceftriaxone plus
azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol. 2007
Jul;110(1):53-60.http://www.ncbi.nlm.nih.gov/pubmed/17601896
Azithromycin (LAP/ SSW/ BUBO): Amsden GW, Gray CL. Serum and WBC pharmacokinetics of 1500 mg of
azithromycin when given either as a single dose or over a 3 day period in healthy volunteers. J Antimicrob Chemother.
2001 Jan;47(1):61-6. http://www.ncbi.nlm.nih.gov/pubmed/11152432
Azithromycin (LAP/ SSW/ BUBO): Sampson MR, Dumitrescu TP, Brouwer KL, Schmith VD. Population
pharmacokinetics of azithromycin in whole blood, peripheral blood mononuclear cells, and polymorphonuclear cells in
healthy adults.CPT Pharmacometrics Syst Pharmacol. 2014 Mar 5;3:e103. http://www.ncbi.nlm.nih.gov/pubmed/24599342
x
Lidocaine 1% without adrenaline (epinephrine): MCC registered package inserts of Kocef® 250 mg, 500 mg, 1 g;
Rociject® 500 mg, 1 g; Oframax® 250 mg, 1 g.
xi
Metronidazole, oral Bignell C, Fitzgerald M; Guideline Development Group; British Association for Sexual Health and HIV
UK. UK national guideline for the management of gonorrhoea in adults, 2011.Int J STD AIDS. 2011 Oct;22(10):541-7.
http://www.ncbi.nlm.nih.gov/pubmed/21998172
Metronidazole, oral: Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2010.MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1-110. Erratum in: MMWR
Recomm Rep. 2011 Jan 14;60(1):18. Dosage error in article text. http://www.cdc.gov/std/treatment/2010/
xii
Azitromycin, oral, 2 g (Severe penicillin allergy): Azithromycin: Pitsouni E, Iavazzo C, Athanasiou S, Falagas ME. Singledose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a metaanalysis of randomised controlled trials. Int J Antimicrob Agents. 2007 Sep;30(3):213-21.
http://www.ncbi.nlm.nih.gov/pubmed/17596917
xiii
Antibiotic therapy for stage II-IV PID: Centers for Disease Control and Prevention. Sexually Transmitted Diseases
Treatment Guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-3): 1-137.
xiv
Antibiotic therapy for stage II-IV PID (Severe pencillin allergy): Centers for Disease Control and Prevention. Sexually
Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-3): 1-137.
xv
TOP option (MVA or medical TOP): Blanchard K, Lince-Deroche N, Fetters T, Devjee J, de Menezes ID, Trueman K,
Sudhinaraset M, Nkonko E, Moodley J. Introducing medication abortion into public sector facilities in KwaZulu-Natal, South
Africa: an operations research study. Contraception. 2015 Oct;92(4):330-8. http://www.ncbi.nlm.nih.gov/pubmed/26162575
xvi
Pethidine, IM: Royal College of Obstetricians and Gynaecologists. The Care of Women Requesting Induced Abortion.
Evidence-based Clinical Guideline Number 7, November 2011.
https://www.rcog.org.uk/globalassets/documents/guidelines/abortion-guideline_web_1.pdf
Pethidine, IM: SAMF, 2014.
xvii
Morphine, IM: SAMF, 2014.
xviii
Misoprostol, PV: Gómez Ponce de León R, Wing D, Fiala C. Misoprostol for intrauterine fetal death. Int J Gynaecol
Obstet. 2007 Dec;99 Suppl 2:S190-3. http://www.ncbi.nlm.nih.gov/pubmed/17961568
Misoprostol, PV: Neilson JP, Gyte GM, Hickey M, Vazquez JC, Dou L. Medical treatments for incomplete miscarriage.
Cochrane Database Syst Rev. 2013 Mar 28;3:CD007223. http://www.ncbi.nlm.nih.gov/pubmed/23543549
Misoprostol, PV: Wildschut H, Both MI, Medema S, Thomee E, Wildhagen MF, Kapp N. Medicalmethods for midtrimester termination of pregnancy. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005216.
http://www.ncbi.nlm.nih.gov/pubmed/21249669
xix
Mifepristone, oral: Royal College Of Obstetricans and Gynaecologists The Care of Women Requesting Induced
Abortion, November 2011.
https://www.rcog.org.uk/globalassets/documents/guidelines/abortion-guideline_web_1.pdf
xx
Levonorgestrol, oral, 1.5 mg: Cheng L, Che Y, Gülmezoglu AM. Interventions for emergency contraception. Cochrane
Database Syst Rev. 2012 Aug 15;8:CD001324. http://www.ncbi.nlm.nih.gov/pubmed/22895920
xxi
Copper IUD: Cheng L, Che Y, Gülmezoglu AM. Interventions for emergency contraception. Cochrane Database Syst
Rev. 2012 Aug 15;8:CD001324. http://www.ncbi.nlm.nih.gov/pubmed/22895920
xxii
STI prophylaxis (Ceftriaxone, IM; lidocaine 1% without adrenaline (epinephrine); azithromycin, oral; metronidazole, oral):
PHC STGs and EML, 2014. http://health.gov.za/
STI prophylaxis (Ceftriaxone, IM; lidocaine 1% without adrenaline (epinephrine); azithromycin, oral; metronidazole, oral):
National Department of Health. STI Guidelines, 2014. http://health.gov.za/
2015
5.17
CHAPTER 6
OBSTETRICS
Note: For medical complications of pregnancy, refer to the relevant
chapters. Only common conditions specific to pregnancy, or requiring special
management in pregnancy are included in this chapter.
6.1 ANAEMIA IN PREGNANCY
O99.0
DESCRIPTION
Haemoglobin (Hb) <11 g/dL. Anaemia in pregnancy is most commonly due to
iron deficiency. Hb levels in pregnancy should be routinely checked on-site at
the first antenatal visit, and again at 28 weeks and 36 weeks. Treatment of
anaemia is generally recommended when the Hb falls below 10 g/dL.
i
LoE:III
GENERAL MEASURES
A balanced diet to prevent nutritional deficiency.
Advise against eating soil, clay, charcoal, and excessive consumption of tea
and coffee.
MEDICINE TREATMENT
Prophylaxis

Ferrous sulphate compound BPC, oral, 170 mg (± 65 mg elemental iron)
daily.
LoE:III
AND

Folic acid, oral, 5 mg daily.
o Continue with iron and folic acid supplementation during lactation.
Iron deficiency (Hb <10g/dL)

Ferrous sulphate compound BPC, oral, 170 mg (± 65 mg elemental iron)
ii
12 hourly.
LoE:I
o Continue for 3–6 months after the Hb reaches
normal to replenish iron stores.
o Hb is expected to rise by at least 1.5 g/dL in two weeks.
o When using iron together with calcium supplementation, ensure that
iron and calcium are taken at least 4 hours apart from one another.
o If Hb has not increased after 4 weeks of therapy, do a FBC to
confirm hypochromic microcytic anaemia.
Parenteral iron
If there is no response to oral iron, and iron deficiency is confirmed, review
adherence to oral iron, and consider:

Iron, IV.
o An initial dose of 600 mg intravenous iron is usually adequate to
raise the Hb to acceptable levels.
2015
6.1
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o
o
OBSTETRICS
Administration varies with the type of parenteral iron preparation.
Consult the package insert for total dose iron infusion. (Iron
sucrose, for example, is administered as follows: 200 mg iron in
200 mL sodium chloride IV, over 30 minutes, given on alternate
days until the total dose has been given).
For markedly anaemic or very obese women, consult the package
insert on the total dose of iron infusion.
LoE:III
REFERRAL/CONSULTATION
No response to management.
6.2 DIABETES MELLITUS IN PREGNANCY
O24
This condition should ideally be managed in consultation with a specialist.
DESCRIPTION
Established diabetes: Diabetes (type 1 or 2) predating pregnancy.
Gestational diabetes (GDM): carbohydrate intolerance first recognised during
pregnancy. It does not exclude the possibility that diabetes preceded the
antecedent pregnancy.
Diagnostic criteria for GDM
Either a fasting plasma glucose ≥ 5.6 mmol/L OR a plasma glucose of ≥ 7.8
mmol/L two hours after a 75 g oral glucose tolerance test.
The following women should be screened for GDM, from 24 weeks gestation
onwards:
» Women of Indian ethnic origin.
2
» BMI >35 kg/m .
» Age > 40 years of age.
» GDM in previous pregnancy.
» Family history (first degree relative) of diabetes.
» Previous unexplained third trimester fetal death.
» Previous baby with birthweight >4 kg.
» Polyhydramnios in index pregnancy.
» Glycosuria (≥1+ glucose in urine).
» A fetus that is large for gestational age.
GENERAL MEASURES
» Stop smoking.
» Moderate exercise.
» Dietary advice.
Elective delivery at about 38 weeks’ gestation.
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6.2
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MEDICINE TREATMENT
The mainstay of therapy is insulin. An initial trial of metformin has a role in the
following patients:
» obese women, and
» women with mild type 2 diabetes.
Even with careful selection, approximately half of patients will require addition
iii
of insulin for adequate glucose control.
LoE:I

Metformin, oral, 500 mg daily.
o Increase dose to 500 mg 12 hourly after 7 days.
o Titrate dose to a maximum of 850 mg 8 hourly according to glucose
control.
o Contra-indications to metformin: liver or renal impairment.
o If not tolerated change to insulin.
Do capillary glucose profiles, i.e. pre-, 1-hour and 2- hour for breakfast, lunch
and supper.
Aim for:
» preprandial values < 5.3 mmol/L
» 1-hour postprandial < 7.8 mmol/L
» 2-hour postprandial < 6.4 mmol/L
iv
LoE:III
Abnormal profiles
Diabetic women should be admitted for poor glucose control, despite
metformin therapy.
Start insulin.
Insulin requirements may increase with increasing gestation and later
readmission may be necessary.
Preferred regimen
Use intermediate acting insulin at bedtime (with a bedtime snack) to maintain
preprandial levels and short acting insulin with all 3 meals to maintain the
post prandial levels.
Starting dose may be based on previous insulin requirements, if known, or
empiric starting dose:
 Insulin, intermediate acting, 12 units at bedtime with a bedtime snack.
 Insulin, soluble, short acting 8 units 30 minutes before each of the three
main meals (breakfast, lunch and supper).
Adjust insulin dosage daily according to blood glucose profiles, until control
is adequate.
LoE:III
Where the above recommended regimen is not feasible
Twice-daily regimen with biphasic insulin.
Empiric starting dose if previous insulin requirements are not known:
 Insulin, biphasic.
o Daily dose: 0.5 units/kg/day, two thirds 30 minutes
before breakfast and one third 30 minutes before
2015
LoE:III
6.3
CHAPTER 6
o
OBSTETRICS
supper.
Titrate to achieve target blood glucose as above.
During labour:
Monitor serum glucose hourly.
Stop subcutaneous insulin.
Administer short acting insulin to maintain physiological blood glucose levels.
 Insulin, short acting, continuous IV infusion, 20 units plus 20 mmol
potassium chloride in 1 L dextrose 5% at an infusion rate of 50 mL/hour,
i.e. 1 unit of insulin/hour
o If blood glucose < 4 mmol/L, discontinue insulin.
o If >7 mmol/L, increase infusion rate to 100 mL/hour
Postpartum insulin requirements decrease rapidly.
During the first 48 hours give insulin 4-hourly according to blood glucose levels.
Resume pre-pregnancy insulin or oral hypoglycaemic regimen once eating a
full diet.
The newborn is at risk of:
» hypoglycaemia,
» respiratory distress syndrome,
» hyperbilirubinaemia, and
» congenital abnormalities.
Postpartum management
Contraception
Tubal ligation should be considered.
Consider:
o Low-dose combined contraceptive in well-controlled cases.
o Progestogen-only preparation or intra-uterine contraceptive device if
planning to breastfeed.
Need for ongoing anti-diabetic therapy
Offer women diagnosed with GDM during the index pregnancy an oral
glucose tolerance test after 6 weeks postpartum to assess whether they
have diabetes needing ongoing therapy.
REFERRAL/CONSULTATION
»
»
»
Obese women,
Excessive fetal growth despite adequate diabetes control.
Poor glucose control despite adequate insulin.
6.3 HEART DISEASE IN PREGNANCY
O75.4
All women with heart disease require referral for specialist evaluation and
risk assessment. The risk is particularly high in women with mechanical
2015
6.4
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OBSTETRICS
valves, Eisenmenger’s syndrome or pulmonary hypertension. Termination of
pregnancy (TOP) is an option for women with severe heart disease if
recommended by a specialist.
GENERAL MEASURES
All pregnant women with haemodynamically significant heart disease require
multidisciplinary management in consultation with both obstetrician and
physician/cardiologist.
Consider thyrotoxicosis, anaemia and infection, which may precipitate cardiac
failure.
Spontaneous delivery is usually preferable to Caesarean section, unless there
are obstetric reasons for surgery.
During labour:
» Nurse in semi-Fowler’s position.
» Avoid unnecessary intravenous fluids.
» Give adequate analgesia.
» Antibiotic prophylaxis for infective endocarditis, guided by the nature of
the heart lesion (for cardiac indications and antibiotic recommendations
see section 3.5: Endocarditis, Infective). Procedures for which
endocarditis prophylaxis is indicated include:
 Vaginal delivery in the presence of suspected infection.
 Caesarean section.
 Assisted vaginal delivery.
 Prelabour rupture of membranes.
» Avoid a prolonged second stage of labour by means of assisted delivery
with forceps (preferably) or ventouse.
» Avoid ergometrine after delivery of the newborn.
» Observe in a high care area for 24 hours post-delivery, as the risk of
pulmonary oedema is highest in this period.
Contraception, including the option of tubal ligation should be discussed
during the antenatal period and after delivery in all women with significant
heart disease.
Women who had life-threatening complications during pregnancy should be
advised not to become pregnant again.
MEDICINE TREATMENT
Indications for full anticoagulation during pregnancy (high risk):
» valvular disease with atrial fibrillation
» mechanical prosthetic heart valves
Pregnant women with mechanical prosthetic valves should not receive
LMWH unless antifactor Xa levels can be monitored reliably weekly.
Therapeutic range is pre-dosing level 0.6 units/mL and a 4-hour peak
level of 1–1.2 units/mL
2015
6.5
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First trimester

Unfractionated heparin, IV, 5 000 units as a bolus.
o Followed by 1 000–1 200 units/hour as an infusion.
OR

Unfractionated heparin, SC, 15 000 units 12 hourly.
o Adjust the dose to achieve a mid-target PTT at 2–3 x control.
Practise strict infection control if using multi-dose vials, with one vial per patient
and use of needle-free adaptor.
Second trimester until 36 weeks

Warfarin, oral, 5 mg daily.
o Adjust dose to keep INR within the therapeutic range of 2.5–3.5 for
mechanical valves, and 2–3 for atrial fibrillation.
After 36 weeks until delivery

Unfractionated heparin, IV, 5 000 units as a bolus.
o Followed by 1 000–1 200 units/hour as an infusion.
OR

Unfractionated heparin, SC, 15 000 units 12 hourly.
o Adjust dose with aPTT to keep it 2 – 3 x control.
o Stop heparin on the morning of elective Caesarean section (6 hours
before scheduled surgery) or when in established labour, and re-start
6 hours after vaginal delivery or 12 hours after Caesarean section, as
long as there is no concern that the patient is bleeding.
Consider the use of warfarin throughout pregnancy for women with older
generation mechanical valves, or valves in the mitral position.
Prophylaxis for venous thromboembolism
» More than one previous episode of venous thromboembolism.
» One previous episode without a predisposing factor, or with evidence of
thrombophilia.

Unfractionated heparin, SC, 5 000 units 12 hourly.
OR

Low molecular weight heparin, e.g.:

Enoxaparin, SC, 40 mg daily.
v
LoE:I
vi
LoE:I
Cardiac failure
See section 3.4: Congestive Cardiac Failure.
Treatment is as for non-pregnant women, except that ACE-inhibitors and
ARBs are contra-indicated.
If a vasodilator is needed:

Hydralazine, oral, 25 mg 8 hourly.
o Maximum dose: 200 mg daily.
2015
6.6
CHAPTER 6
OBSTETRICS
AND

Isosorbide dinitrate, oral, 20 mg 12 hourly.
o Maximum dose: 160 mg daily.
Delivery
Contraction and retraction of the uterus after delivery increases the total
peripheral resistance, and causes a relative increase in circulating volume.
This may precipitate pulmonary oedema.
In women with NYHA grade II dyspnoea or more, consider the use of
furosemide:

Furosemide, IV, 40 mg with delivery of the baby.
o Monitor for 48 hours thereafter for pulmonary oedema.
6.4 HYPERTENSIVE DISORDERS IN PREGNANCY
O15.9
DESCRIPTION
Hypertensive disorders are one of the most common direct causes of maternal
mortality and are responsible for significant perinatal and maternal morbidity.
These disorders include chronic hypertension, pre-eclampsia, eclampsia and
HELLP Syndrome. Early detection and timely intervention is essential to
prevent maternal and perinatal complications.
Preeclampsia
Preeclampsia is hypertension with significant proteinuria developing for the
first time after 20 weeks of gestation, and can also be superimposed on
chronic hypertension - evidenced by the new onset (after 20 weeks’
gestation) of persistent proteinuria in a woman who had an initial diagnosis
of chronic hypertension.
Mild to moderate pre-eclampsia:
A diastolic BP of 90-109 mmHg and/or systolic BP of 140-159 mmHg, with
≥1+ proteinuria; and no organ dysfunction.
Severe pre-eclampsia:
» Acute severe hypertension (diastolic BP of 110 mmHg and/or systolic
> 160 mmHg) and ≥ 1+ proteinuria.
OR
» Any degree of hypertension & proteinuria with evidence of organ
dysfunction
(renal
dysfunction,
raised
liver
enzymes,
thrombocytopaenia).
GENERAL MEASURES
Bed rest, preferably in hospital.
Lifestyle adjustment and diet.
2015
6.7
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OBSTETRICS
Monitor BP, urine output, renal and liver function tests, platelet count,
proteinuria and fetal condition.
Consider delivery when risks to mother outweigh risks of prematurity to baby.
MEDICINE TREATMENT
Treatment
Antihypertensives
Medicine treatment will be dictated by blood pressure response.
Monitor progress until a stable result is achieved.
In general, diuretics are contra-indicated for hypertension in pregnant women.
When needed, combine drugs using lower doses when BP >160/100 mmHg,
before increasing single medication doses to a maximum.
vii
LoE:III

Methyldopa, oral, 250 mg 8 hourly as a starting dose.
o Increase to 500 mg 6 hourly, according to response.
o Maximum dose: 2 g/day.
AND/OR

Amlodipine, oral, 5 mg daily.
o Increase to 10 mg daily.
Hypertensive emergency
SBP ≥160 mmHg and/or DBP ≥110 mmHg. Admit to a high-care setting for
close monitoring.

Nifedipine, oral, 10 mg.
o Repeat after 30 minutes if needed, until systolic blood pressure <160
mmHg and diastolic blood pressure < 110 mmHg.
o Swallow whole. Do not chew, bite or give sublingually.
viii
LoE:III
If unable to take oral or inadequate response:

Labetalol, IV infusion, 2 mg/minute to a total of 1–2 mg/kg.
o Reconstitute solution as follows:
- Discard 40mL of sodium chloride 0.9% from a 200 mL container.
- Add 2 vials (2 x 100 mg) of labetalol (5 mg/mL) to the remaining
160 mL of sodium chloride 0.9% to create a solution of 1 mg/mL.
- Start at 40mL/hour to a maximum of 160 mL/hour.
- Titrate against BP – aim for BP of 140/100 mmHg.
o Once hypertensive crisis has been resolved, switch to an oral
preparation.
ix
LoE:I
Delivery

Oxytocin, IM, 10 units as a single bolus after delivery of the baby.
x
LoE:III
Ergot-containing medicines are contraindicated in hypertensive women,
including pre-eclampsia, following delivery of the baby.
2015
6.8
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OBSTETRICS
Pre-eclamptic and eclamptic women are often hypovolaemic, particularly
when the haematocrit exceeds 40%, but are also susceptible to pulmonary
oedema. Consequently, hypotension is a risk during anaesthesia. Careful
infusion of IV fluids is important. Limit blood-loss at Caesarean section.
Prevention of pre-eclampsia
For women at high risk of pre-eclampsia, e.g. pre-eclampsia in a previous
pregnancy, chronic hypertension, diabetes, antiphospholipid syndrome or SLE,
from 12 weeks gestation onwards:

Aspirin, oral, 75–150 mg daily with food.

Calcium, oral.
o For high-risk patients: Calcium carbonate, oral, 500 mg 12 hourly
(equivalent to 1 g elemental calcium daily).
o Although the benefit is greatest in high-risk women, consider use of
this agent in all pregnant women.
o When using iron together with calcium supplementation, ensure that
iron and calcium are taken at least 4 hours apart from one another.
6.5 SEVERE PRE-ECLAMPSIA AND ECLAMPSIA
O15
DESCRIPTION
Generalised tonic-clonic seizures after 20 weeks of pregnancy and within 7
days after delivery, associated with hypertension and proteinuria. Exclude any
other obvious cause of the seizure before making the diagnosis. Management
will include preventing further seizures, controlling the blood pressure, referral
to a high-care unit and delivery of the baby if not already post-delivery.
GENERAL MEASURES
Place patient in left-lateral position.
Clear airway. If necessary, insert oropharyngeal airway.
MEDICINE TREATMENT
If necessary:

Oxygen via nasal prongs or face mask to maintain a saturation of >90%.
To prevent eclamptic seizures, magnesium sulphate is recommended for
patients with severe pre-eclampsia, including imminent eclampsia. In some
cases this allows for delivery to be delayed to improve neonatal outcome.
When used for prevention of eclampsia, magnesium sulphate is administered
for 24 hours, and then stopped. The same dose regimens are used as for
eclampsia. Women with severe pre-eclampsia should be managed under
specialist care.
2015
6.9
CHAPTER 6
OBSTETRICS
Treatment
In high-care setting:

Magnesium sulphate, IV, 4 g in 200 mL sodium chloride 0.9% over 20
minutes (loading dose).
Follow with:

Magnesium sulphate, IV infusion, 1 g/hour until 24 hours after delivery, or
after the last convulsion (maintenance dose).
Where infusion pumps are not available:

Magnesium sulphate, IV, 4 g in 200 mL sodium chloride 0.9% over 20
minutes.
Follow with:

Magnesium sulphate, IM, 5 g every 4 hours different IM sites, until 24
hours after delivery or following the last convulsion.
Stop magnesium sulphate if knee reflexes become absent or if urine output
< 100 ml/ 4 hours or respiratory rate <16 breaths/minute.
If respiratory depression occurs:

Calcium gluconate 10%, IV, 10 mL given slowly at a rate not exceeding
5 mL/minute.
Recurrent eclamptic seizure despite magnesium sulphate loading
dose administration:

Magnesium sulphate, IV, 2 g over 10 minutes.
For agitated and restless women with eclampsia:

Lorazepam, IV/IM, 4 mg.
o Maximum dose: 8 mg.
OR
Clonazepam, IV, 2 mg.
o May be repeated after 5 minutes.
o Maximum dose: 4 mg.
OR
If above not available:
Diazepam, IV, 10–20 mg, not faster than 2 mg/minute.
Notify the person who will resuscitate the newborn that a benzodiazepine
and/or magnesium has been given to the mother.
REFERRAL
Refer all eclampsia cases to a high or intensive care facility.
2015
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OBSTETRICS
6.6 CHRONIC HYPERTENSION
O10.9
GENERAL MEASURES
Lifestyle modification
No alcohol should be taken.
Regular moderate exercise, e.g. 30 minutes brisk walking at least 3 times a
week.
Smoking cessation.
Aim to keep BP < 140/90 mmHg.
Screen for end-organ damage.
Fetal surveillance by symphysis-fundus height (SFH) growth.
Ask mother about fetal movements at each antenatal visit.
Consider labour induction if:
» BP persistently  160/110 mmHg, or
» pregnancy of ≥ 37 weeks duration, or
» in the presence of maternal or fetal compromise, e.g. poor SFH growth
and oligohydramnios, etc.
MEDICINE TREATMENT
See prevention and treatment of pre-eclampsia.
Switch ACE-inhibitors and diuretics to methyldopa and/or amlodipine. Women
should be advised that there’s an increased risk of congenital abnormalities if
ACE-inhibitors were taken during pregnancy.
6.7 HIV IN PREGNANCY
O98.7
For comprehensive information on the care of HIV-infected pregnant women,
refer to the current National consolidated guidelines for the prevention of
mother-to-child transmission of HIV (PMTCT) and the management of HIV in
children, adolescents and adults, April 2015.
All pregnant women should receive routine counselling and voluntary HIV
testing at their very first antenatal visit.
All women who test negative should be offered repeat HIV testing every 3
months throughout pregnancy, at labour/delivery, at the 6-week EPI visit and 3
monthly throughout breastfeeding.
HIV infected pregnant women upon diagnosis, should be clinically staged, and
have a blood sample taken for CD4 cell count and serum creatinine taken on
the same day. The result must be obtained within a week.
Postpartum contraceptive use should be discussed in the antenatal period.
All mothers should be educated during the antenatal period about the benefits
2015
6.11
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OBSTETRICS
of breastfeeding.
The patient should have a TB symptom screen at each visit, with further TB
investigations if any of the answers to the screening questions are positive.
Patients should be screened and treated for syphilis and other STIs, in line
with basic antenatal care.
Lifelong ART should be initiated in all pregnant or breastfeeding women on the
same day of diagnosis regardless of CD4 count or infant feeding practice.
Adequate support and counselling, particularly addressing ART adherence,
should be given.
Women with unwanted pregnancies < 20 weeks’ gestation should be assisted
with access to TOP services.
MEDICINE TREATMENT
» Patients should receive ART at the first antenatal visit, whether newly
diagnosed or known to be living with HIV but not on ART.
» If standard first-line ART is contraindicated, these patients are considered
to have high-risk pregnancies and require urgent referral to HIV/ART
services.
Administer:
 AZT, oral 300 mg 12 hourly, until alternative combination ART can be
initiated.
» Perform a baseline ALT and serum creatinine at commencement of ART.
» Tenofovir should not be used in pregnant women with a calculated
creatinine clearance or eGFR of < 60 mL/minute or a serum creatinine ≥
85 µmol/L (the latter is a more sensitive measure of renal impairment in
pregnancy).
» Partner testing and routine cervical cancer screening should be done.
FIRST-LINE ART REGIMENS
1st ANC visit
All pregnant women not
on ART (any
gestational age).
AND
All breastfeeding
women not on ART.

TDF, oral, 300 mg
daily.
AND
 FTC, oral, 200 mg
daily
AND
 EFV, oral, 600 mg at
night.
Provided as a fixed dose
combination (FDC).
2015
If there is a
contraindication to the
FDC, start AZT
immediately and refer
patient for individual
medicines.
Contraindication to TDF:
renal insufficiency.
Contraindication to EFV:
active psychiatric illness.
6.12
CHAPTER 6
Pregnant women
currently on ART
OBSTETRICS
Continue current ART
regimen.
Do a VL as soon as
pregnancy is confirmed.
Pregnant women with
confirmed 2nd or 3rd line
ART regimen failures
should not breastfeed
their infants, if they can
safely formula feed.
2nd ANC visit (1 week later)
Creatinine ≤ 85
Continue FDC:
micromol/L
TDF+FTC+EFV
Creatinine > 85
Stop FDC:
micromol/L
TDF+FTC+EFV.
(TDF is contraindicated)
Replace TDF with ABC:
 ABC, oral, 600 mg
daily.
Active psychiatric
illness
(EFV may be
contraindicated. Consult
an HIV specialist and/or
psychiatrist)

TDF, oral, 300 mg
daily.
AND
 FTC, oral, 200 mg
daily
AND
 NVP, oral, 200 mg
daily for 2 weeks, then
200 mg 12 hourly (OR
LPV/r 400/100 mg 12
hourly).
High-risk pregnancy: refer
urgently for alternate triple
therapy within 2 weeks
with dose adjustment if
indicated and
investigation of renal
dysfunction.
CD4 ˂ 250
 Replace EFV with
NVP, oral 200 mg
daily for 2 weeks,
then 200 mg 12
hourly.
o Do an ALT test
before starting NVP.
NVP should not be
used in women with
elevated ALT.
o If ALT elevated,
replace EFV with
LPV/r, oral, 400/100
mg 12 hourly.
CD4 ≥ 250
 Replace EFV with
LPV/r, oral, 400/100
mg 12 hourly.
xi
LoE:III
Caesarean Section:
All pregnant women, including HIV infected pregnant women should
receive a single dose of antibiotic prophylaxis (See chapter 11: Surgical
2015
6.13
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OBSTETRICS
antibiotic prophylaxis).
Women with the following risk factors are at higher risk of infection post
Caesarean section:
» Advanced immunosuppression.
» Prolonged rupture of membranes.
» Multiple vaginal examinations (> 5 PVs).
» Second stage CS.
Monitor carefully and treat infection appropriately.
HIV infected pregnant women in labour not on ART:

NVP, oral, 200 mg as a single dose.
AND
 TDF, oral, 300 mg as a single dose.
AND
 FTC, oral, 200 mg as a single dose.
For more information regarding HIV management, see section 10.1:
Antiretroviral Therapy.
6.8 SYPHILIS
A53.9
DIAGNOSTIC CRITERIA
Positive syphilis serology (RPR titre ≥16).
GENERAL MEASURES
Inform contact(s).
MEDICINE TREATMENT
Mother
 Benzathine benzylpenicillin (depot formulation), IM, 2.4 million units weekly
for 3 doses.
Note: If the mother has received <3 doses, the baby should be treated for congenital
syphilis.
Severe penicillin allergy
For penicillin sensitive pregnant women: penicillin desensitisation.
(See page xxviii for detailed information).
2015
6.14
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OBSTETRICS
Oral penicillin desensitisation regimen.
A: Reconstitute phenoxymethylpenicillin 250mg/ 5mL
Step
Medicine mg/mL
Amount to administer (mL)
B: To make 0.5 mg/mL solution
Strictly every 15 minutes
Dilute 0.5 mL of reconstituted phenoxymethylpenicillin
solution in 49.5 mL water.
1
0.1 mL
2
0.2 mL
0.5 mg/mL solution
3
0.4 mL
(1000 units/mL)
4
0.8 mL
5
1.6 mL
6
3.2 mL
7
6.4 mL
C: To make 05 mg/mL solution
Dilute 1 mL of reconstituted phenoxymethylpenicillin
solution in 9 mL water.
8
1.2 mL
5 mg/mL solution
9
2.4 mL
(10000 units/mL)
10
4.8 mL
D: Reconstituted phenoxymethylpenicillin
250mg/ 5mL = 50 mg/mL
11
1.0 mL
50 mg/mL
12
2.0 mL
(80000 units/mL)
13
4.0 mL
14
8.0 mL
After step 14, observe for 30 minutes, then 1.0 g IV.
Interval between doses: 15 minutes.
Asymptomatic, well baby:
Mother has syphilis and has not been treated, or was only partially treated:

Benzathine benzylpenicillin (depot formulation), IM, 50 000 units/kg as a
single dose into the antero-lateral thigh.
Symptomatic baby

Procaine penicillin, IM, 50 000 units/kg daily for 10 days. (Not for I.V. use).
OR
Benzylpenicillin (Penicillin G), IV, 50 000 units/kg, 12 hourly for 10 days.
6.9 JAUNDICE IN PREGNANCY
O26.6
DESCRIPTION
The most common causes of jaundice in pregnancy are not pregnancyspecific. They include viral hepatitis, and adverse drug reactions.
Pregnancy-specific causes include:
» intrahepatic cholestasis of pregnancy,
» acute fatty liver of pregnancy (acute yellow atrophy of the liver),
» severe pre-eclampsia or eclampsia, and
2015
6.15
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»
OBSTETRICS
hyperemesis gravidarum.
REFERRAL
All, as certain causes of jaundice in pregnancy have a high mortality.
6.10 HYPEREMESIS GRAVIDARUM
O21.9
DESCRIPTION
Recurrent vomiting leading to ketosis, generally in the first trimester.
Exclude:
» medical causes, e.g. thyrotoxicosis, and
» molar pregnancy.
GENERAL MEASURES
Counselling.
Frequent small, dry meals.
Avoid fatty and spicy foods.
Restrict oral intake for 24–48 hours, but ensure adequate intravenous
hydration.
MEDICINE TREATMENT
Correct electrolyte imbalance with IV fluids.
 Pyridoxine, oral, 25 mg 8 hourly.
AND
 Metoclopramide, oral/IV, 10–20 mg 6 hourly as needed.
AND
 Vitamin B complex, IV, 10 mL.
In refractory cases:
Administer daily until hyperemesis is controlled:
 Dexamethasone, IM/IV, 4–8 mg daily.
AND
 Ondansetron, IV, 4–8 mg over 5 minutes, daily.
6.11 PRETERM LABOUR (PTL) AND PRETERM
PRELABOUR RUPTURE OF MEMBRANES (PPROM)
O60/O42
DESCRIPTION
Preterm: < 37 weeks gestation.
Most problems occur at < 34 weeks’ gestation.
Confirm ruptured membranes by sterile vaginal speculum.
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OBSTETRICS
Preterm labour confirmed by regular uterine contractions with progressive
cervical changes.
GENERAL MEASURES
Assess fetal wellbeing.
Estimate fetal weight.
Deliver if chorio-amnionitis suspected.
MEDICINE TREATMENT
If gestation < 34 weeks:
Pre-hydrate before administration of nifedipine:
 Sodium chloride 0.9%, IV, 200 mL.
AND
 Nifedipine, oral, 20 mg.
o
If contractions persist, follow with 10 mg after 30 minutes then 10 mg
4 hourly for up to 48 hours.
If gestation < 32 weeks and where nifedipine contra-indicated:

Indomethacin, oral, 50 mg immediately then 25 mg 4 hourly for up to 48
xii
hours.
LoE:I
Note: Indomethacin may cause oligohydramnios, and its
use is associated with a risk of premature closure of the ductus arteriosus.
Use only if there is intolerance to nifedipine.
To improve fetal lung maturity at 26–34 weeks:
 Betamethasone, IM, 12 mg, 2 doses 12 hours apart.
xiii
If betamethasone is not available:
 Dexamethasone, IM, 8 mg, 3 doses 8 hours apart.
LoE:I
xiv
LoE:III
Note: Corticosteroids are maximally effective from 24 hours after
administration of the first dose. Therefore give as soon as possible following
diagnosis of PTL or PPROM.
Antibiotic therapy
Indicated routinely for ruptured membranes and only selectively for preterm
labour with intact membranes at high risk of infection.
 Amoxicillin, oral, 500 mg 8 hourly for 5 days.
AND
 Metronidazole, oral, 400 mg 8 hourly for 5 days.
xv
Severe penicillin allergy:
 Azithromycin, oral, 500 mg daily for 3-5 days
AND
 Metronidazole, oral, 400 mg 8 hourly for 5 days.
LoE:I
xvi
LoE:III
Prepare for appropriate care of preterm infant.
2015
6.17
CHAPTER 6
OBSTETRICS
REFERRAL
»
Fetus requiring neonatal intensive care, e.g. weight <1.5 kg or gestation
< 32 weeks.
Fetus requiring specialised treatment after birth, e.g. surgery.
Severely ill mother.
»
»
6.12 SUPPRESSION OF LABOUR FOR FETAL DISTRESS
O62.9
DESCRIPTION
Tocolysis is useful to treat fetal distress in labour and to suppress labour in
women needing transfer or awaiting Caesarean section. Also used prior to
external cephalic version.
MEDICINE TREATMENT

Salbutamol bolus, 250 mcg IV, slowly over 2 minutes.
o Reconstitute the solution as follows:
– Add 1 mL (i.e. 0.5 mg/mL) salbutamol to 9 mL sodium chloride
0.9% to create a solution of 50 mcg/mL.
– Monitor pulse. Do not administer if mother has cardiac disease.
– Place the mother in the left lateral position.
xvii
LoE:I
6.13 LABOUR INDUCTION
O80
If induction of labour is indicated, for medical reasons, for example preeclampsia, diabetes, or post-term pregnancy.
GENERAL MEASURES
Counsel the woman about the risks: failed induction or uterine
hyperstimulation syndrome, which may require emergency Caesarean section.
Cervix favourable and confirmed HIV-uninfected mother
Artificial rupture of the membranes.
Cervix unfavourable
Extra-amniotic Foley catheter with/without saline infusion: recommended if
attempts at ripening the cervix with prostaglandins fail.
Pass a Foley catheter with 30 mL bulb through cervix with sterile technique.
Inflate bulb with 50 mL water or sodium chloride 0.9%.
Tape catheter to thigh with light traction.
Alternatively, attach sodium chloride 0.9% 1 L with giving set to catheter, and
infuse sodium chloride 0.9% at 50 mL/hour. Remove after 24 hours.
LoE:III
2015
6.18
CHAPTER 6
OBSTETRICS
MEDICINE TREATMENT
Cervix favourable
Amniotomy (if HIV negative) followed 2 hours later by:

Oxytocin, IV, 2 units in 200 mL sodium chloride 0.9%
o Start at an infusion rate of 12 mL/hour (i.e. 2 milliunits /minute). If
absent or inadequate contractions, increase infusion rate according
to the table below:
Time after starting
(minutes)
Oxytocin dose
(milliunits/minute)
0
30
60
90
120
150
180
210
2
4
6
8
10
12
16
20
Dilution: 2 units in 200
mL sodium chloride
0.9% (mL/hour)
12
24
36
48
60
72
96
120
Note:
» Avoid oxytocin in women with previous Caesarean section or parity ≥ 5.
» Continuous electronic fetal heart rate monitoring is essential.
» Aim for adequate uterine contractions (3–5 contractions in 10 minutes).
Once adequate contractions achieved, do not increase rate further.
» Most women will experience adequate contractions at a dose of 12
milliunits/minute.
» If tachsystole develops (> 5 contractions in 10 minutes), reduce or stop
the oxytocin infusion to achieve 3-5 contractions in 10 minutes. If there
are fetal heart rate abnormalities which persist despite stopping the
oxytocin, administer salbutamol as above.
Cervix unfavourable
Prostaglandins, e.g.:
 Dinoprostone gel, intravaginally, 1 mg.
o Repeat after 6 hours.
o Do not exceed 4 mg.
OR
 Dinoprostone tablets, intravaginally, 1 mg.
o Repeat after 6 hours.
o Do not exceed 4 mg.
xviii
LoE:III
Note: Perform a non-stress test (NST), before starting the induction, and
cardiotocography (CTG) within an hour of each dinoprostone insertion, to
evaluate the fetal condition during labour induction.
OR
2015
6.19
CHAPTER 6
OBSTETRICS
 Misoprostol, oral, 20 mcg 2 hourly until in labour, or up to 24 hours.
o Oral misoprostol may be given as freshly made-up solution of one
200 mcg tablet in 200 mL water, i.e. 1 mcg/mL solution. Give 20
mL of this solution 2 hourly.
o Stop misoprostol administration when in established labour.
o Maximum 24 hours.
o If no response, consider induction with 50 mL bulb Foley catheter
with or without extra-amniotic saline infusion.
o Never use oxytocin and misoprostol simultaneously.
o Misoprostol and other prostaglandins are contraindicated in
women with previous Caesarean sections and in grand
multiparous women.
Note:
» Misoprostol in larger doses than indicated here for labour induction at
term, may cause uterine rupture.
» Only to be prescribed by a doctor experienced in Maternal Health.
» A non-stress test to be done an hour after each new dose of 4-hourly
during misoprostol administration.
6.14 LABOUR PAIN, SEVERE
GENERAL MEASURES
Antenatal counselling.
Psychological support from family member, friend or volunteer ‘doula’.
The need for analgesics may be reduced by keeping the woman informed
about the progress of labour, providing reassurance and carefully explaining
the procedures performed.
Anticipate the need for analgesia rather than waiting for severe distress.
MEDICINE TREATMENT

Pethidine, IM, 1 mg/kg 4 hourly as needed, to a maximum of 100 mg.
OR

Morphine, IM, 0.1 mg/kg 4 hourly as needed, to a maximum of 10 mg.
xix
LoE:III
Titrate dose and dose frequency according to pain.
Supplement with premixed nitrous oxide 50%/ oxygen 50% in late first stage.
Epidural anaesthesia
Offer this service only at hospitals with anaesthetic expertise, monitoring,
capacity and equipment for epidural. (See chapter 12: Anaesthesiology, pain
and intensive care).
Perineal analgesia:
 Lidocaine, 1 or 2%, infiltration, locally or by a pudendal block.
2015
6.20
CHAPTER 6
OBSTETRICS
Postpartum and post-episiotomy pain

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
OR

Ibuprofen, oral, 400 mg 8 hourly with meals.
OR

Pethidine, IM, 1 mg/kg 4 hourly as needed, to a maximum of 100 mg.
OR

Morphine, IM, 0.1 mg/kg 4 hourly as needed, to a maximum of 10 mg.
xx
LoE:III
6.15 DEHYDRATION/KETOSIS IN LABOUR
E86
DESCRIPTION
Subclinical dehydration is often missed in labour.
GENERAL MEASURES
Encourage adequate oral fluid intake.
MEDICINE TREATMENT
Mild dehydration
Give oral fluids.
Moderate/severe dehydration
Administer intravenous fluids, e.g.:

Sodium chloride 0.9%, IV, 250 mL/hour.
Re-evaluate hydration hourly.
6.16 POSTPARTUM FEVER
O75.2
DESCRIPTION
During delivery the woman's protective barrier against infections is
temporarily reduced and this may lead to infections.
The cause of fever may be a serious complication.
Consider excessive use of misoprostol for PPH (doses >600 mcg) as a
possible non-infectious cause of postpartum fever.
GENERAL MEASURES
Prevent deep vein thrombosis.
Complete evacuation of uterine contents.
Hysterectomy may be indicated in severe uterine sepsis.
Attention to breast engorgement.
2015
6.21
CHAPTER 6
OBSTETRICS
MEDICINE TREATMENT
Antibiotic treatment, where appropriate, should be guided by the presumed
source of infection.
Empiric antibiotic therapy

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly, until patient apyrexial for
24 hours.
Follow with:
LoE:III

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
6.17 POSTPARTUM HAEMORRHAGE
O72
DESCRIPTION
Blood loss >500 mL after birth of the baby or any blood loss which is regarded
as excessive.
GENERAL MEASURES
Bimanual compression of the uterus.
Ensure delivery of placenta.
Check for local causes of bleeding.
Balloon tamponade of the uterine cavity should be considered if the patient is
to be transferred to another facility.
MEDICINE TREATMENT
Prevention
rd
Active management of the 3 stage of labour:

Oxytocin, IM, 10 units.
AND
Controlled cord traction.
Treatment
Resuscitate.
Put up two IV lines.

Oxytocin, IV, 20 units in 1 L sodium chloride 0.9% at 250 mL/hour.
If necessary:
ADD

Ergometrine, IM, 0.2–0.5 mg.
OR

Oxytocin, IM, 5 units.
AND

Ergometrine, IM, 0.5 mg.
o Repeat ergometrine as needed up to a maximum of 1 mg in 24 hours.
2015
6.22
CHAPTER 6
o
OBSTETRICS
Avoid ergometrine in women with hypertension or cardiac disease,
except in severe cases where the benefit is considered to outweigh
the risk (discuss with a specialist).
For non-responding cases:

Dinoprost 5 mg/mL, intramyometrial.
o Dilute 1 mL to 10 mL.
o Give 2 doses of 1 mL of dilute solution at different sites.

Tranexamic acid 1 g, IV, slowly over 10 minutes.
In settings where oxytocin had NOT been administered as prophylaxis at birth:

Misoprostol, sublingual, or rectal, 600 mcg as a single dose.
xxi
LoE:I
6.18 THE RHESUS NEGATIVE WOMAN
O36.0
GENERAL MEASURES
Maternal serum antibodies absent
Prevention
Test for maternal serum antibodies at ‘booking’, 28 and 34 weeks’ gestation.
During pregnancy, give prophylactic anti-D immunoglobulin to the mother
within 72 hours of a potentially sensitising event.
MEDICINE TREATMENT
After a termination of pregnancy (TOP), miscarriage, ectopic pregnancy or
amniocentesis:

Anti-D immunoglobulin, IM, 100 mcg.
After external cephalic version:

Anti-D immunoglobulin, IM, 100 mcg.
At birth, determine the Rh status of the cord blood and request a Coomb’s test:
Cord blood Rh negative - no treatment.
Cord blood Rh positive, Coomb’s negative:

Anti-D immunoglobulin, IM, 100 mcg.
If a large feto-maternal transfusion is suspected:

Anti-D immunoglobulin, IM, 300 mcg for every 30 mL transfusion.
o Maximum dose: 1 200 mcg.
AND
Do a maternal blood Kleihauer test.
Rh positive, Coomb’s positive:
In these cases the mother will also have antibodies.
Do not administer anti-D immunoglobulin.
2015
6.23
CHAPTER 6
OBSTETRICS
Maternal serum antibodies present
Consult a specialist.
6.19 URINARY TRACT INFECTION (UTI) IN PREGNANCY
6.19.1 CYSTITIS
N30
DESCRIPTION
This condition usually presents with lower abdominal pain, frequency of
micturition, and/or dysuria. There are no features of sepsis, e.g. fever. Urine
dipstick testing usually shows nitrites, with/without leukocytes; protein and/or
blood may also be detected.
GENERAL MEASURES
Encourage oral fluid intake.
Midstream urine for microscopy, culture and sensitivity.
MEDICINE TREATMENT
Empiric treatment (nitrites positive OR leukocytes positive on dipstick):
 Amoxicillin/clavulanic acid 875/125 mg, oral, 12 hourly for 5 days.
Severe penicillin allergy:
 Fosfomycin 3 g, oral, as a single dose.
xxii
LoE:III
REFFERAL/CONSULTATION
No response to treatment, or resistant organism on culture.
6.19.2 PYELONEPHRITIS, ACUTE
N10
DESCRIPTION
This condition is more serious and may result in preterm labour.
Features of pyelonephritis include:
º
» temperature ≥38 C
» renal angle tenderness (often bilateral)
» other features of sepsis, i.e. vomiting, tachypnoea, tachycardia,
confusion and hypotension
GENERAL MEASURES
»
»
»
Admit to hospital.
Ensure adequate hydration with intravenous fluids, up to 3 L of sodium
chloride 0.9% over 24 hours.
Midstream urine for microscopy, culture and sensitivity.
2015
6.24
CHAPTER 6
OBSTETRICS
MEDICINE TREATMENT
Empiric therapy:
 Ceftriaxone, IV, 1 g, daily for 48 hours, or until fever subsides.
OR
 Gentamicin, IV, 6 mg/kg, daily (ensure normal renal function).
Switch to oral therapy as soon as the patient is able to take oral fluids:
 Amoxicillin/clavulanic acid, oral, 875/125 mg 12-hourly for 7 days.
Change antibiotics according to culture and sensitivity results
After treatment, ensure that 2 urine specimens are negative to confirm
eradication.
REFFERAL/CONSULTATION
»
»
»
Failure to respond to antibiotics.
Impaired renal function.
Abnormal urinary tract
References:
i
National Department of Health. Guidelines for maternity in South Africa, 2015. http://www.health.gov.za/
ii
Ferrous sulphate compound BPC: Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for irondeficiency anaemia in pregnancy. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD003094.
http://www.ncbi.nlm.nih.gov/pubmed/21975735
iii
Insulin (supplemental to metformin): Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial
Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med.
2008 May 8;358(19):2003-15. http://www.ncbi.nlm.nih.gov/pubmed/18463376
iv
Target glucose levels: NICE. Diabetes in pregnancy: management of diabetes and its complications from
preconception to the postnatal period, 25 February 2015. http://nice.org.uk/guidance/ng3
v
Unfractionated heparin: Phung OJ, Kahn SR, Cook DJ, Murad MH. Dosing frequency of unfractionated heparin
thromboprophylaxis: a meta-analysis. Chest. 2011 Aug;140(2):374-81.
http://www.ncbi.nlm.nih.gov/pubmed/21349929
vi
Enoxaparin: Wein L, Wein S, Haas SJ, Shaw J, Krum H. Pharmacological venous thromboembolism prophylaxis
in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Jul
23;167(14):1476-86. http://www.ncbi.nlm.nih.gov/pubmed/17646601
vii
Antihypertensive combination therapy: Hypertension guideline working group, Seedat YK, Rayner BL, Veriava
Y. South African hypertension practice guideline 2014. Cardiovasc J Afr. 2014 Nov-Dec;25(6):288-94.
http://www.ncbi.nlm.nih.gov/pubmed/25629715
viii
Nifedipine (dosing interval): Prevost RR, Akl SA, Whybrew WD, Sibai BM. Oral nifedipine pharmacokinetics in
pregnancy-induced hypertension. Pharmacotherapy. 1992;12(3):174-7.
http://www.ncbi.nlm.nih.gov/pubmed/1951561
Nifedipine (dosing interval): Committee on Obstetric Practice. Committee Opinion No. 623: Emergent therapy
for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2015
Feb;125(2):521-5. http://www.ncbi.nlm.nih.gov/pubmed/25611642
Nifedipine (dosing interval): Mol BW, Roberts CT, Thangaratinam S, Magee LA, de Groot CJ, Hofmeyr GJ.
Pre-eclampsia. Lancet. 2015 Sep 2. pii: S0140-6736(15)00070-7. http://www.ncbi.nlm.nih.gov/pubmed/26342729
ix
Labetalol, IV infusion: Raheem IA, Saaid R, Omar SZ, Tan PC. Oral nifedipine versus intravenous labetalol for
acute blood pressure control in hypertensive emergencies of pregnancy: a randomised trial. BJOG. 2012
Jan;119(1):78-85. http://www.ncbi.nlm.nih.gov/pubmed/21985500
x
Oxytocin, IM: National Department of Health. Guidelines for maternity in South Africa, 2015.
http://www.health.gov.za
xi
ART regimens (pregnancy): National department of health South Africa. National consolidated guidelines for the
prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents
and adults. April 2015. http://www.health.gov.za/
xii
Indomethacin: Reinebrant HE, Pileggi-Castro C, Romero CL, Dos Santos RA, Kumar S, Souza JP, Flenady V.
Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2015 Jun
5;6:CD001992. http://www.ncbi.nlm.nih.gov/pubmed/26042617
xiii
Betamethasone, IM: Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for
women at risk of preterm birth. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004454.
2015
6.25
CHAPTER 6
OBSTETRICS
http://www.ncbi.nlm.nih.gov/pubmed/16856047
Betamethasone, IM: Royal College of Obstetricians and Gynaecologists. Green-top Guideline No.7: Antenatal
corticosteroids to reduce neonatal morbidity and mortality. October 2010. Available at:
https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_7.pdf
xiv
Dexamethasone, IM: Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids
and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst
Rev. 2013 Aug 29;8:CD006764. http://www.ncbi.nlm.nih.gov/pubmed/123990333
Dexamethasone, IM: Royal College of Obstetricians and Gynaecologists. Green-top Guideline No.7: Antenatal
corticosteroids to reduce neonatal morbidity and mortality. October 2010. Available at:
https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_7.pdf
xv
Amoxicillin, oral: Pattinson RC, Makin JD, Funk M, Delport SD, Macdonald AP, Norman K, Kirsten G, Stewart C,
Woods D, Moller G, Coetzee E, Smith P, Anthony J, Schoon M, Grobler S. The use of dexamethasone in women
with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial.
Dexiprom Study Group. S Afr Med J. 1999 Aug;89(8):865-70. http://www.ncbi.nlm.nih.gov/pubmed/10488363
Metronidazole, oral: Pattinson RC, Makin JD, Funk M, Delport SD, Macdonald AP, Norman K, Kirsten G,
Stewart C, Woods D, Moller G, Coetzee E, Smith P, Anthony J, Schoon M, Grobler S. The use of dexamethasone
in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled,
randomised trial. Dexiprom Study Group. S Afr Med J. 1999 Aug;89(8):865-70.
http://www.ncbi.nlm.nih.gov/pubmed/10488363
xvi
Azithromycin: Contract circular HP02-2015AI. http://www.health.gov.za/
xvii
Salbutamol, IV: Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour.
Cochrane Database Syst Rev. 2014 Feb 5;2:CD004352. http://www.ncbi.nlm.nih.gov/pubmed/24500892
Salbutamol, IV:
xviii
Dinoprostone: SAMF, 2014
xix
Pethidine, IM: SAMF, 2014.
Morphine, IM: SAMF, 2014.
xx
Pethidine, IM: SAMF, 2014.
Morphine, IM: SAMF, 2014.
xxi
Misoprostol: Essential Steps in Managing Obstetric Emergencies (ESMOE), facilitator’s guide.
Misoprostol: Hofmeyr GJ, Gülmezoglu AM, Novikova N, Linder V, Ferreira S, Piaggio G. Misoprostol to prevent
and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related
effects. Bull World Health Organ. 2009 Sep;87(9):666-77. http://www.ncbi.nlm.nih.gov/pubmed/19784446
Misoprostol: Department of Health, Republic of South Africa. 2015. Guidelines for Maternity care in South
Africa, 5th edition. http://www.health.gov.za/
Misoprostol: International Federation Of Gynecology And Obstetrics. Treatment of postpartum hemorrhage with
misoprostol. Int J Gynaecol Obstet. 2012 Dec;119(3):215-6. http://www.ncbi.nlm.nih.gov/pubmed/23036964
xxii
Amoxicillin/clavulanic acid, oral: Lewis DA, Gumede LY, van der Hoven LA, de Gita GN, de Kock EJ, de Lange
T, Maseko V, Kekana V, Smuts FP, Perovic O. Antimicrobial susceptibility of organisms causing communityacquired urinary tract infections in Gauteng Province, South Africa. S Afr Med J. 2013 Mar 15;103(6):377-81.
http://www.ncbi.nlm.nih.gov/pubmed/23725955
Fosfomycin, oral: Lewis DA, Gumede LY, van der Hoven LA, de Gita GN, de Kock EJ, de Lange T, Maseko V,
Kekana V, Smuts FP, Perovic O. Antimicrobial susceptibility of organisms causing community-acquired urinary tract
infections in Gauteng Province, South Africa. S Afr Med J. 2013 Mar 15;103(6):377-81.
http://www.ncbi.nlm.nih.gov/pubmed/23725955
2015
6.26
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL
DISORDERS
7.1 NEPHROLOGY DISORDERS
CAUTION
Check all medicines for possible dose adjustment based on eGFR/CrCl.
The doses of many medicines need to be adjusted in renal impairment.
Recommendations for medicines that require dose adjustment in renal
impairment can be found in the SAMF, package insert, and from many
online resources e.g.: http://www.globalrph.com/index_renal.htm
7.1.1 CHRONIC KIDNEY DISEASE (CKD)
N18.9
DESCRIPTION
»
»
Structural or functional kidney damage present for > 3 months, with or
without a decreased estimated glomerular filtration rate (eGFR).
Markers of kidney damage include:
- proteinuria or haematuria
- increased serum creatinine or low eGFR
- small kidneys on ultrasound
- abnormalities renal biopsy
eGFR calculator online access:
https://www.kidney.org/apps/professionals/egfr-calculator
Common causes of CKD include:
» hypertension
» diabetes mellitus
» polycystic kidney disease
» HIV/AIDS
» glomerular disease (idiopathic, hepatitis B and C, systemic lupus
erythematosus, etc.)
Chronic kidney disease can be entirely asymptomatic
until over 75% of kidney function is lost.
TREATMENT AND PREVENTION STRATEGIES ACCORDING TO STAGES
Adverse outcomes of CKD can often be prevented or delayed through early
detection and treatment of risk factors for CKD.
2015
7.1
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
In patients with CKD, the stage of disease should be assigned based on the
level of kidney function according to the classification below, irrespective of
diagnosis.
Adults with early CKD i.e. stages 0–3 can all be managed at primary care
level once the cause and plan for care has been established.
All stage 4 and 5 patients require referral/consultation with a specialist.
Staging of kidney disease
Stage/
glomerular
filtration rate
(mL/minute/1.73m2)
Description
Stage 0
or
eGFR > 90
» At increased risk
Stage 1
or
eGFR > 90
of CKD e.g.:
- diabetes
mellitus
- hypertension
- glomerular
disease
- HIV
» Kidney damage
with normal
eGFR.
Action
Includes actions
from preceding
stages
» Screening for
CKD and CVD.
» CKD and CVD
risk reduction.
» Treat
hypertension,
diabetes, HIV.
» Diagnose and
»
»
Stage 2
or
eGFR 60–89
» Kidney damage
»
with mild ↓ eGFR
»
»
Stage 3
or
eGFR 30–59
» Moderate ↓ eGFR
treat comorbid
conditions.
Slow
progression.
CVD risk
reduction.
Investigate
cause.
Develop care
plan.
Monitor
progression.
» Evaluate and
Frequency of
follow up of
kidney disease
in a stable
patient
» Annual urine
dipstix.
» Annual
measurement
of potassium,
creatinine and
eGFR.
» Annual urine
dipstix.
» Annual
»
»
»
treat for
complications.
»
»
2015
measurement
of potassium,
creatinine and
eGFR.
Annual urine
dipstix
Annual
measurement
of potassium,
creatinine and
eGFR
Frequency of
monitoring
must increase
when
approaching
Stage 4 or
when eGFR
shows rapid
decline.
3-6 monthly:
clinical
assessment.
3-6 monthly
testing of Hb,
urea,
7.2
CHAPTER 7
Stage 4
or
eGFR 15–29
Stage 5
or
ESRD
or
eGFR < 15
or
on dialysis
NEPHROLOGICAL/UROLOGICAL DISORDERS
» Severe ↓ eGFR
» Refer for
consideration of
renal
replacement
therapy.
» Kidney failure
requiring renal
replacement
therapy
» End Stage Renal
Disease (ESRD)
» Refer for
consideration of
renal
replacement
therapy, i.e.
dialysis or
transplant if
uraemia present.
creatinine,
potassium,
calcium,
phosphate.
» 3 monthly
clinical
assessment.
» 3 monthly
testing of Hb,
urea,
creatinine,
potassium,
calcium,
phosphate,
PTH.
ON RRT:
» Monthly testing
of Hb.
» 3 monthly
clinical
assessment.
» 3 monthly
testing of urea,
calcium,
creatinine,
PTH,
potassium, HIV
phosphate, and
Hepatitis B.
GENERAL MEASURES
»
Address cardiovascular disease risk factors. See section 3.1 Ischaemic
heart disease and atherosclerosis, prevention.
» Limit salt intake.
» Limit dietary protein intake to 0.6 g/kg/day
» Avoid nephrotoxic medicines like NSAIDs.
» Screen for proteinuria.
- If urine dipstick 1+ or greater, repeat on a properly collected
midstream urine specimen on another occasion.
- If proteinuria persists quantify protein with a spot urine protein
creatinine ratio. Significant proteinuria = spot urine protein
creatinine ratio of > 0.1 g/mmol.
- If urine dipstick less than 1+, request albumin creatinine ratio.
Patients differ in their ability to excrete a salt and water load and therefore
fluid balance should be individualised.
2015
7.3
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
MEDICINE TREATMENT
The following interventions may delay progression of renal disease.
Proteinuria reduction
The ideal targets are: protein creatinine ratio < 0.03 g/mmol or albumin
creatinine ratio (ACR) < 2.2 mg/mmol. Most benefit is achieved by reducing
protein creatinine ratio to < 0.1 g/mmol or ACR < 100 mg/mmol.

Start treatment with a low dose of ACE-inhibitor and titrate up to the
maximum tolerated dose, e.g.
 Enalapril, oral.
o Start with 5 mg 12 hourly and titrate to 20 mg 12 hourly, if tolerated.
o Monitor creatinine and potassium after 2 weeks if eGFR < 60
mL/minute and after 4 weeks if eGFR > 60 mL/minute.
o If creatinine increases by >20% from the baseline, stop ACEinhibitor and consult a specialist.
i
LoE:III
If an ACE-inhibitor is not tolerated due to intractable cough:

Consider an angiotensin II receptor blocker (ARB), e.g.:
ii
LoE:III
 Losartan, oral,
o Start with 50 mg daily and titrate to 100 mg daily, if
tolerated.
o ARBs are contra-indicated following ACE-inhibitor-associated
iii
angioedema.
LoE:I
CAUTION
ACE-inhibitors and ARBs can cause or exacerbate hyperkalaemia in CKD.
Check the serum potassium before starting these medicines, and monitor
serum potassium on therapy.
Hypertension
Optimise BP control with additional antihypertensive agents, BP control
results in a lowering of proteinuria and slower decline in eGFR.
Target BP: 130/80 mmHg.
See section 3.6: Hypertension.
Hyperlipidaemia
If hyperlipidaemia is a co-existent cardiovascular risk factor, manage
according to section 3.1 Ischaemic heart disease and atherosclerosis,
prevention.
Diabetes mellitus
In diabetics, optimise control according to section 8.5: Diabetes mellitus.
In diabetics with kidney disease there is an increased risk of hypoglycaemia.
2015
7.4
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Insulin is the safer option to control blood glucose in patients with eGFR <
60 mL/minutes.
Note:
» Insulin requirements will decrease as renal disease progresses.
» Stop glibenclamide when eGFR < 60 mL/minute because of an
increased risk of hypoglycaemia.
» Reduce metformin dose when eGFR < 60 mL/minute (maximum dose
500 mg 12 hourly).
» Discontinue metformin when eGFR < 30 mL/minute because of the risk
of lactic acidosis.
iv
LoE:III
Fluid overload and oedema
 Furosemide, oral, 40 mg 12 hourly.
When fluid overloaded and eGFR < 60 mL/minute, start:
 Furosemide, oral, 40 mg 12 hourly.
o Titrate to a maximum of 500 mg 12 hourly.
o Furosemide is ineffective when patients are on dialysis and anuric.
Hypocalcaemia and hyperphosphataemia
The aim is to lower phosphate levels and maintain normal calcium levels to
ensure calcium phosphate product (i.e. Ca x PO4) <4.4, to prevent calcium
deposition in vessels and tissue which aggravates vascular disease.
Restrict dietary phosphate intake. (Dietitian consultation)
https://unckidneycenter.org/files/kidney-health-library-files/renaldiet_phosphorus.pdf
Patients with CKD stage 3–5, not on dialysis:
Hyperphosphataemia and/or hypocalcaemia:

Calcium carbonate, oral, equivalent to elemental calcium, 500 mg 8
hourly with meals, increase to 1 g 8 hourly with meals, if
hyperphosphatemia persists.
Hypocalcaemia and low or normal serum phosphate:

Calcium carbonate, oral, equivalent to elemental calcium, 500 mg 8
hourly between meals, increase to 1 g 8 hourly between meals.
In patients with CKD stage 5 who are not candidates for renal replacement
therapy, the benefits of phosphate binding are unclear, and regular PTH
monitoring is not necessary.
Patients considered suitable candidates for renal replacement therapy:
++
Monitor Ca , PO4 and PTH levels, as per table: Staging of kidney disease.
For hyperphosphataemia uncontrolled on calcium carbonate:
 Aluminium hydroxide BP (300 mg/5 mL), oral, 10 mL 8 hourly. Specialist
initiated.
2015
7.5
CHAPTER 7
o
NEPHROLOGICAL/UROLOGICAL DISORDERS
To prevent dementia-associated aluminium toxicity, do not use for
longer than 3 months.
For hyperparathyroidism, initiate when PTH levels > 2 times upper limit of
normal range:
 Calcitriol, oral, 0.25–4 mcg daily. Specialist initiated.
LoE:III
Anaemia associated with CKD in patients on dialysis
programmes
Patients on chronic haemodialysis or peritoneal dialysis are often anaemic
due to iron deficiency and deficiency of erythropoietin.

Iron, elemental, oral. See section 2.2 Anaemia, iron deficiency
o If no response consider parenteral iron.
AND
 Erythropoietin, SC/IV.
Definitive treatment, e.g. transplantation, usually improves anaemia. It is
important to identify factors likely to aggravate anaemia, e.g. iron deficiency
and infection.
Acidosis and hyperkalaemia
Specialist consultation for possible renal replacement therapy.
CONSULT WITH A SPECIALIST AT THE LOCAL REFERRAL
CENTRE
»
»
»
»
»
CKD stage 3 and above.
Unknown cause of kidney failure.
Rapid deterioration in renal function.
Resistant hypertension despite appropriate medication and adherence.
All ESRD patients who may qualify for long term dialysis programs. See
section 7.1.7: Renal replacement therapy.
7.1.2
GLOMERULAR
SYNDROME
DISEASE
AND
NEPHRITIC
N01.9/N03.9
DESCRIPTION
Acute glomerulonephritis presents with one or more of the following:
haematuria, proteinuria, an acute decrease in eGFR, fluid retention, and
hypertension.
GENERAL MEASURES
»
Give oxygen, and nurse in semi-Fowlers position if patient has respiratory
distress.
» Early consultation with a specialist.
2015
7.6
CHAPTER 7
»
»
»
NEPHROLOGICAL/UROLOGICAL DISORDERS
Regulate fluid and electrolyte balance. Monitor weight closely.
Dietary modification if severe kidney dysfunction, e.g. restrict salt,
protein, potassium and phosphate intake.
Avoid potential nephrotoxins: e.g. NSAIDs, aminoglycosides.
MEDICINE TREATMENT
Fluid overload

Furosemide, as a slow IV bolus, 80 mg.
o Avoid unnecessary intravenous fluids.
If hypertension present:
Diastolic BP > 100 mmHg or systolic BP is >150 mmHg:
 Amlodipine, oral, 5 mg as a single dose.
AND
 Hydrochlorothiazide, oral, 25 mg (if eGFR ≥ 30 mL/min).
OR
Furosemide, oral, 40–80 mg (if eGFR < 30 mL/min).
Check all medicines for possible dose adjustments.
http://www.globalrph.com/index_renal.htm
CONSULTATION/REFERRAL
The management of glomerular disease is individualised and management
of all patients should be discussed with a specialist.
7.1.3
NEPHROTIC SYNDROME
N04.9
DESCRIPTION
Glomerular disease characterised by:
» severe proteinuria, i.e.: protein:creatinine ratio >0.25 g/mmol
and
- oedema,
- hypoalbuminaemia, and
hyperlipidaemia.
The cause cannot be determined accurately without a biopsy.
GENERAL MEASURES
Regulate salt and fluid intake.
Weigh regularly to assess fluid retention.
Check for postural hypotension to identify excessive diuresis.
Evaluate proteinuria with protein creatinine ratio:
» initially – weekly
» when discharged – monthly, until stable
Monitor potassium frequently for patients on ACE-inhibitors and/or diuretics.
2015
7.7
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
MEDICINE TREATMENT
Management should be guided by a specialist.
CONSULTATION/REFERRAL
All patients.
7.1.4 ACUTE KIDNEY INJURY
N17.9
DESCRIPTION
Acute kidney injury (AKI) is generally detected by an increase in the serum
creatinine and/or a decrease in urine output.
Kidney injury may be due to a combination of factors.
GENERAL MEASURES
A detailed history and good clinical examination is necessary to identify
potentially reversible causes.
Avoid any nephrotoxic medicines e.g. NSAIDs, aminoglycosides. Check all
medicines for possible dose adjustments.
MEDICINE TREATMENT
Fluid overload
In patients with fluid overload where dialysis is not immediately available, a
short trial of furosemide in consultation with a specialist may be appropriate.
LoE:III
Acute dialysis
Discuss all cases with the referral centre.
Common indications for acute dialysis include:
» Pulmonary oedema and anuria.
» Intractable metabolic acidosis and severe hyperkalaemia (> 7 mmol/L).
» Uraemic complications, e.g. pericarditis, encephalopathy and bleeding.
» Medication overdose if due to dialysable toxin. See section 19:
Exposure to poisonous substances.
Note: HIV infection is not a contra-indication for acute dialysis.
Both haemodialysis and peritoneal dialysis are acceptable modalities of
therapy in the acute setting.
Peritoneal dialysis fluid is potentially infectious for HIV and viral hepatitis.
Hyperkalaemia
Serum K+ >6.5 mmol/L.
Emergency measures
 Calcium gluconate 10%, slow IV bolus, 10 mL over 10 minutes.
2015
7.8
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
o Maximum dose: 40 mL.
Dextrose 50%, continuous IV infusion, 100 mL with soluble insulin, 10
units administered over 15–30 minutes.
o Monitor blood glucose levels hourly.
AND
 Salbutamol 0.5%, solution, nebulised.
o Dilute 1 mL in 4 mL of sodium chloride 0.9%.

These are short term measures. Patients should then either be dialysed or if
this is not feasible:
 Sodium polystyrene sulfonate, oral, 15 g with 15 mL lactulose, 6 hourly.
OR
 Sodium polystyrene sulfonate, rectal, 30–60 g as an enema.
o After 8 hours, wash out with phosphate enema.
Note: Rectal administration is less effective.
LoE:III
Some patients do not recover kidney function and should be
treated as CKD.
7.1.5 RENAL REPLACEMENT THERAPY
Z49
Refer to the current National Department of Health Guidelines for renal
dialysis.
PATIENT SELECTION
The final decision for selection of patients for renal replacement therapy
should be made by a multidisciplinary team using standardised selection
criteria.
The ideal patient for renal replacement therapy has uncomplicated CKD
stage 5 (ESRD), and is a suitable candidate for renal transplantation.
Individual renal units have their own criteria for acceptance and these may
include:
» presence of systemic illnesses,
» age,
» BMI, and
» psychosocial factors.
Obtain these guidelines from the referral centre.
7.2 MAJOR ELECTROLYTE ABNORMALITIES
7.2.1 HYPERKALAEMIA
E87.5
See section 7.1.4: Acute kidney injury.
2015
7.9
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NEPHROLOGICAL/UROLOGICAL DISORDERS
7.2.2 HYPOKALAEMIA
E87.6
DESCRIPTION
A serum potassium level < 3.5 mmol/L.
Mild to moderate symptoms: muscle weakness and cramps.
Severe symptoms: rhabdomyolysis, paralysis, dysrhythmias, diaphragmatic
weakness.
It is usually due to gastro-intestinal (vomiting, diarrhoea) or renal losses
(diuretic therapy, hyperaldosteronism).
MEDICINE TREATMENT
For chronic asymptomatic hypokalaemia, look for and manage the cause:

Potassium chloride, oral, 600 mg, 1-2 tablets 8 hourly.
o Titrate to response to therapy.
o Maximum daily dose: 6 g (i.e.10 tablets per day in divided doses).
o Review potassium levels after 4 weeks.
Note: Routine supplementation with potassium chloride in patients who are on
diuretics is usually inappropriate. Co-administration of ACE-inhibitors and/or
spironolactone counteracts the hypokalaemia from furosemide or thiazides.
For mild to moderate hypokalaemia in a non-vomiting patient. (Potassium
level usually 3-3.4 mmol/L):

Potassium chloride, oral, 600 mg, 1-2 tablets 8 hourly.
o Titrate to response to therapy.
o Maximum daily dose: 6 g.
o Each 600 mg potassium chloride tablet contains 8 mmol of
potassium chloride.
o Continue treatment until the serum potassium concentration is
persistently above 3.5 mmol/L and symptoms or signs have
resolved.
v
LoE:III
For severe symptomatic hypokalaemia:

Potassium chloride, IV, 40 mmol in 1 L of 0.9% or 0.45% sodium
chloride, mixed thoroughly.
o Administer at a maximum rate of 20 mmol per hour over 3 hours.
Beware of volume overload.
o Potassium chloride 15%, 10 mL ampoule contains 20 mmol of
vi
potassium.
LoE:III
Reduce the rate of intravenous potassium repletion or change to oral
therapy once the hypokalaemia is no longer severe. Continue treatment until
the serum potassium concentration is persistently above 3.5 mmol/L and
symptoms or signs have resolved.
If not responding to therapy, check for hypomagnesaemia.
2015
7.10
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
7.2.3 HYPERNATRAEMIA
E87.0
DESCRIPTION
A serum sodium level > 145 mmol/L.
» Mild to moderate symptoms:
Lethargy, weakness, irritability
» Severe symptoms:
Convulsions, coma
It is usually due to inadequate water intake (decreased thirst sensation or
unable to drink water) or to gastro-intestinal (vomiting, diarrhoea) or renal
losses (diabetes insipidus, osmotic diuresis, furosemide) of water.
GENERAL MEASURES
Treat the cause.
Calculate the water deficit:
Water deficit = (total body water)*(1-(140/Na))
Total body water = correction factor * weight.
(The correction factor is 0.6 for men, 0.5 for women and elderly men,
and 0.45 for elderly women).
Online calculator: http://www.nephromatic.com/water_deficit.php
MEDICINE TREATMENT
Correction fluid:

Dextrose 5%, IV infusion.
o Monitor for hyperglycaemia. Rate of correction of hypernatraemia
should be slower than 10 mmol/L over 24 hours to prevent cerebral
oedema.
o Ongoing obligatory water loss through skin and stool (estimated at
30 mL/hour) must also be replaced.
vii
LoE:III
Desired water replacement in the first 24 hours =
Water deficit x 10 mmol/L ÷ (Serum [Na] – 140)
Hourly infusion rate =
Desired water replacement in the first day ÷ 24 hours +
30 mL per hour
7.2.4 HYPONATRAEMIA
E87.1
DESCRIPTION
A serum sodium level < 135 mmol/L.
Mild to moderate symptoms:
Headache, nausea, vomiting, fatigue,
gait disturbances, and confusion
Severe symptoms:
Seizures, obtundation, coma, and
respiratory arrest.
2015
7.11
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Acute hyponatraemia develops within hours due to self-inflicted waterintoxication.
\
Rapid correction may lead to central pontine myelinolysis, which is often
irreversible. Sodium should be frequently monitored and increases should be
<9 mmol/L per day.
APPROACH
2015
7.12
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
MEDICINE TREATMENT
In the presence of fluid overload:

Furosemide, oral, 40 mg 12 hourly.
o Increase dose to control signs of fluid overload and to improve
viii
hyponatraemia.
LoE:III
In the absence of fluid overload:
Consult with a specialist before administering sodium chloride, IV
infusion.

Sodium chloride, IV infusion.
One litre
of NaCl
infusate
5% NaCl
Total Na
(mmol/l)
855
Expect an
increase
of 2-3
mmol/L
for every
60mL
0,9% NaCl
» Sodium level < 120
mmol/L
or
» Severe
symptoms(i.e.
seizures,
obtundation, coma,
and respiratory
arrest).
or
» Acute hyponatraemia
due to water
intoxication.
Expect an
increase
of 2-3
mmol/L
for every
60mL
5% NaCl
Indication
855
» Sodium level <120
mmol/L with mild to
moderate symptoms.
or
» Chronic
hyponatraemia
154
» Sodium level > 120
mmol/L
» Dehydrated.
» Asymptomatic or
mild symptoms.
Fluid
 Hypertonic
sodium
chloride, 5%,
60 mL as an
IV bolus over
15 min.
o If symptoms
persist/
worsens or
sodium is
not
improving,
consult a
specialist.
 Hypertonic
sodium
chloride, 5%,
30 mL as an IV
bolus over 15
min.
 Sodium
chloride,
0.9%, IV
infusion, 1L 8
hourly.
Aim
» Symptom
relief.
» Correct
hyponatraemia:
- 4-6 mmol/L
immediately
AND
- Maximum 8
mmol/L in
1st 24 hrs.
» Symptomatic
relief.
» Correct
hyponatraemia:
- Maximum 8
mmol/L in
1st 24 hrs.
» Rehydration.
ix
LoE:III
To calculate the infusion rate, consult a specialist.
http://reference.medscape.com/calculator/hyponatraemia-correctioninfusate-rate
2015
7.13
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
7.3 UROLOGY SECTION
7.3.1 HAEMATURIA
R31.9
DESCRIPTION
Bleeding from the urinary tract, which can be from the kidneys, collecting
system, bladder, prostate and urethra.
REFERRAL
Suspected glomerular disease.
2015
x
LoE:III
7.14
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
7.3.2 URINARY TRACT INFECTION (UTI)
N39.0
DESCRIPTION
Uncomplicated UTI involves either the lower or upper urinary in a nonpregnant woman with a normal urinary tract. UTIs in other groups of patients
are complicated by definition.
Upper UTIs are more serious infections requiring longer and sometimes
intravenous antibiotic treatment.
Features of upper UTI include:
» flank pain/tenderness,
º
» temperature ≥38 c or higher,
» other features of sepsis, i.e. tachypnoea, tachycardia, confusion and
hypotension, or
» vomiting.
In complicated, recurrent or upper UTIs, mid-stream urine should be sent for
microscopy, culture and sensitivity.
MEDICINE TREATMENT
Women with recurrent UTIs should be advised to:
» void bladder after intercourse and before retiring at night
» not postpone voiding when urge to micturate occurs
» change from use of diaphragm to an alternative type of contraception
Empirical treatment is indicated only if:
» positive leucocytes and nitrites on urine test strips on freshly passed
urine, or
» leucocytes or nitrites with symptoms of UTI, or
» systemic signs and symptoms.
Alkalinising agents are not recommended as many antibiotics require a
lower urinary pH.
Uncomplicated community acquired cystitis
 Ciprofloxacin, oral, 500 mg 12 hourly for 3 days.
Complicated community acquired cystitis
 Ciprofloxacin, oral, 500 mg 12 hourly for 7 days.
xi
LoE:III
For pregnant women:
 Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 7 days.
st
Severe penicillin allergy in 1 trimester:

Fosfomycin, oral, 3 g as a single dose dissolved in a glass of water.
xii
LoE:I
2015
7.15
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
nd
rd
Severe penicillin allergy in 2 and 3 trimester:
 Nitrofurantoin, oral, 100 mg 12 hourly for 7 days.
o Avoid near term (38 to 42 weeks) and consider fosfomycin in these
xiii
cases.
LoE:III
Adjust antibiotics according to urine microscopy, culture and sensitivity
results in complicated, recurrent or upper UTIs.
Acute pyelonephritis
Admit all patients with vomiting, sepsis or diabetes.
Ensure adequate hydration with intravenous fluids.
If there is a poor response, perform an ultrasound on all hospitalised patients
urgently as in-patients.
Adjust antibiotic according to sensitivity.
Duration of antibiotic therapy in uncomplicated pyelonephritis:
» fluoroquinolones 7 days
» other antibiotics 14 days.
Longer courses of therapy, 2–3 weeks, should be given for complicated
pyelonephritis.
Patients who have features of severe sepsis or who are vomiting, initiate IV
therapy and switch to oral therapy as soon as clinical condition improves:
If normal renal function:
 Gentamicin, IV, 6 mg/kg daily.
Switch to oral therapy as soon as the patient is able to take oral fluids,
according to microscopy culture and sensitivity results:
 Ciprofloxacin, oral, 500 mg 12 hourly for 7 days.
If impaired renal function:
 Ceftriaxone, IV, 1 g daily.
Switch to oral therapy as soon as the patient is able to take oral fluids,
according to microscopy culture and sensitivity results:
 Ciprofloxacin, oral, 500 mg 12 hourly for 7 days.
o CrCl: < 10 mL/minute: 50% of normal dose.
REFFERAL/CONSULTATION
Urgent
» Acute pyelonephritis in pregnant women.
» Acute pyelonephritis with:
- vomiting
- sepsis
- diabetes mellitus
- urinary tract obstruction on ultrasound
2015
7.16
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Non-urgent
» Failure to improve within 72 hours.
» Women beyond reproductive age.
» > 3 uncomplicated UTIs within a one-year period.
» > 1 complicated UTI within a one-year period.
7.3.3 RECURRENT UTI
N39.0
DESCRIPTION
Recurrence of a UTI > 3 times within a one-year period.
Send urine for microscopy, culture and sensitivity as treatment is determined
by the results.
GENERAL MEASURES
Women should void soon after intercourse.
Identify and treat hormone-deficient atrophic vulvo-vaginitis in the elderly.
MEDICINE TREATMENT
Prophylaxis
To reduce risk of recurrence in patients with >3 infections/year requires
continuous prophylaxis for 6 months:
 Cotrimoxazole 80/400 mg, oral, 1 tablet at night.
OR
 Nitrofurantoin, oral, 100 mg at night.
o Beware of pulmonary fibrosis.
o Limit to 6 months only.
2–3 infections/year:
 Ciprofloxacin, oral, 500 mg as single dose for symptomatic infections
(self-treatment).
UTI in relation to sexual activity:
 Ciprofloxacin, oral, 500 mg as single dose.
Treatment
Treat according to microscopy, culture and sensitivity.
REFERRAL/CONSULTATION
»
»
»
»
»
Failure to respond to prophylactic treatment.
Uncertain diagnosis.
Recurrent infections where no facilities exist for adequate culture of
urine.
All complicated recurrent UTIs.
STI pathogens.
2015
7.17
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
7.3.4 PROSTATITIS
N41.0/N41.1
DESCRIPTION
Clinical features include:
» pyrexia,
» acute pain in the pelvis and perineum,
» dysuria and frequency,
» urinary retention or difficulty, and
» acutely tender prostate on rectal examination.
Chronic non-bacterial prostatitis
This is a diagnosis of exclusion, i.e. failure to respond to antibiotics. It is
associated with perineal, suprapubic, penile and testicular pain.
MEDICINE TREATMENT
Acute bacterial prostatitis
If there are features of associated urethritis (STI regimen):
 Ceftriaxone, IM, 250 mg as a single dose.
AND
 Azithromycin, oral, 1 g as a single dose.
xiv
LoE:III
xv
LoE:I
If there are no features of associated urethritis:
 Ciprofloxacin, oral, 500 mg 12 hourly for 14 days.
Chronic/relapse/persistent infection:
 Ciprofloxacin, oral, 500 mg 12 hourly for 28 days.
REFERRAL
To
»
»
»
LoE:III
LoE:III
urologist if:
No response to treatment.
Urinary retention present.
Chronic/relapsing prostatitis.
7.3.5 BENIGN PROSTATIC HYPERPLASIA
N40.9
DESCRIPTION
Benign prostatic hyperplasia is a noncancerous (benign) growth of the
prostate gland. It usually occurs in men over 50 years of age.
May be associated with both obstructive (weak, intermittent stream and
urinary hesitancy) and irritative (frequency, nocturia and urgency) voiding
symptoms.
Digital rectal examination reveals a uniform enlargement of the prostate.
2015
7.18
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Urinary retention with a distended bladder may be present in the absence of
severe symptoms, therefore it is important to palpate for an enlarged bladder
during examination.
GENERAL MEASURES
Consult with a urologist:
Annual follow-up.
For patients presenting with urinary retention, insert a urethral catheter.
Stop medication that may aggravate urinary retention e.g. tricyclics.
MEDICINE TREATMENT


Alpha blocker, e.g.:
Tamsulosin, oral, 0.4 mg daily.
xvi
LoE:I
7.3.6 OVERACTIVE BLADDER
N39.4
DESCRIPTION
A clinical syndrome consisting of urinary frequency (both daytime and night)
and urgency, with or without urgency incontinence,
GENERAL MEASURES
Urine dipstix to exclude a UTI.
Health education.
Avoid caffeine containing, alcoholic and carbonated beverages.
Pelvic floor muscle training: three sets of 8-12 contractions sustained for 810 seconds each, performed three times a day. Patients should continue for
at least 15-20 weeks.
MEDICINE TREATMENT
For detrusor hyperactivity:
 Oxybutynin, oral, 2.5–5 mg 8 hourly. Specialist initiated.
LoE:III
REFERRAL
»
»
»
For confirmation of diagnosis.
Complications.
Not responding to medical therapy.
7.3.7 ERECTILE DYSFUNCTION
N48.4/F52.2
DESCRIPTION
The inability to attain and maintain an erect penis with sufficient rigidity for
vaginal penetration.
Many cases are psychogenic.
2015
7.19
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Organic causes include neurogenic, vasculogenic or endocrinological
disorders; many systemic diseases; pelvic trauma/surgery; and certain
medicines.
GENERAL MEASURES
Thorough medical and psychosexual history
Examination should exclude gynaecomastia, testicular atrophy or penile
abnormalities.
Review all medicines and, if possible, withdraw medicines that may be
associated with erectile dysfunction
Advise cessation of smoking and excessive alcohol use.
MEDICINE TREATMENT
Treat the underlying condition.
In patients with proven testosterone deficiency:
 Testosterone. Specialist initiated.
See section 8.3: Androgen deficiency.
REFERRAL
»
To a urologist or appropriate specialist if surgical intervention is needed,
e.g. penile prostheses, vascular surgery and pelvic fractures.
7.3.8 RENAL CALCULI
N20.2
DESCRIPTION
A kidney stone or calculus which has formed in the renal tract, i.e. pelvis,
ureters or bladder, as a result of urine which is supersaturated with a stoneforming salt.
Clinical features of obstructing urinary stones may include:
» sudden onset of acute colic, localized to the flank, causing the patient to
move constantly,
» nausea and vomiting,
» referred pain to the scrotum or labium as the stone moves down the
ureter.
Urinalysis usually reveals microscopic or macroscopic haematuria.
Stones may be passed spontaneously, after medical or invasive treatment
If available, collect the stones and send to the laboratory for analysis.
GENERAL MEASURES
Acute stage:
Oral fluids administered liberally.
Intravenous fluids to ensure adequate hydration and urine flow.
2015
7.20
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
To prevent recurrence:
Avoid dehydration.
If recurrences occur, consult a specialist.
MEDICINE TREATMENT
Analgesia for renal colic:

NSAID, oral: e.g.

Ibuprofen, oral, 400 mg 8 hourly with meals.
Note: Avoid NSAIDs if renal impairment is present or
suspected.
xvii
LoE:I
If patient is vomiting:

Diclofenac, IM, 75 mg as a single dose.
AND/OR

LoE:III
Tramadol, IM, 50–100 mg, 6 hourly.
LoE:III
OR

Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Currently, there is no convincing evidence to support the use of hyoscine, in
this setting.
For vomiting:

Metoclopramide, IM, 10 mg 8 hourly.
LoE:III
REFERRAL
»
»
»
In acute setting for suspected or diagnosed obstruction and/or ongoing
pain.
Complicating urinary tract sepsis.
Recurrent calculi.
References:
i
ACE-inhibitor (e.g. enalapril): South African Renal Society Recommendations for the Early detection and
management of CKD in South Africa. http://www.sa-renalsociety.org/guidelines.asp
ACE-inhibitor (e.g. enalapril): The National Kidney Foundation Kidney Disease Outcomes Quality Initiative
(KDOQI) Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification
PART 9. Approach to chronic kidney disease using these guidelines.
http://www2.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm
ACE-inhibitor (e.g. enalapril): South African Renal Society Guidelines for the Optimal Care of Patients on
Chronic Dialysis in South Africa, revised 2011. http://www.sa-renalsociety.org/guidelines.asp
ii
Angiotensin II receptor blocker (e.g. Losartan): South African Renal Society Recommendations for the Early
detection and management of CKD in South Africa.http://www.sa-renalsociety.org/guidelines.asp
Angiotensin II receptor blocker (e.g. Losartan): The National Kidney Foundation Kidney Disease Outcomes
Quality Initiative (KDOQI) Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and
Stratification PART 9. Approach to chronic kidney disease using these guidelines.
http://www2.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm
Angiotensin II receptor blocker (e.g. Losartan): South African Renal Society Guidelines for the Optimal Care of
2015
7.21
CHAPTER 7
NEPHROLOGICAL/UROLOGICAL DISORDERS
Patients on Chronic Dialysis in South Africa, revised 2011. http://www.sa-renalsociety.org/guidelines.asp
iii
Angiotensin II receptor blocker (alternative in ACE-inhibitor induced angioedema): Beavers CJ, Dunn SP,
Macaulay TE. The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitorinduced angioedema. Ann Pharmacother. 2011 Apr;45(4):520-4. http://www.ncbi.nlm.nih.gov/pubmed/21427294
iv
Metformin: PHC STGs and EML, 2014. http://health.gov.za/
Metformin: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA, Ganie YN,
Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt NS, May WM,
Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR, Rheeder P,
Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the Management of Type 2
Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
Metformin: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes
Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J
Diabetes 2013;37(suppl 1):S1-S212. http://www.ncbi.nlm.nih.gov/pubmed/24070961
Metformin: NICE Clinical Guideline 87: Type 2 diabetes - The management of type 2 diabetes, 2009, 2014.
www.nice.org.uk/Guidance/CG87
Metformin: Aronoff, Bennett et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children,
5th Edition. American College of Physicians. United States of America, 2007.
Metformin: Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal
insufficiency. Diabetes Care. 2011 Jun;34(6):1431-7. http://www.ncbi.nlm.nih.gov/pubmed/21617112
v
Potassium chloride, oral: SAMF, 2014.
Potassium chloride, oral: Rastegar A, Soleimani M. Hypokalaemia and hyperkalaemia. Postgrad Med J. 2001
Dec;77(914):759-64. Review. Erratum in: Postgrad Med J 2002 Feb;78(916):126. Rastergar A [corrected to
Rastegar A]. http://www.ncbi.nlm.nih.gov/pubmed/8250319
Potassium chloride, oral: Wong KC, Schafer PG, Schultz JR. Hypokalemia and anesthetic implications. Anesth
Analg. 1993 Dec;77(6):1238-60. Review. Erratum in: Anesth Analg 1994 May;78(5):1035.
http://www.ncbi.nlm.nih.gov/pubmed/8250319
vi
Potassium chloride, IV: SAMF, 2014.
vii
Dextrose 5%, IV: Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med. 2000 May 18;342(20):1493-9.
Review. http://www.ncbi.nlm.nih.gov/pubmed/10816188
Dextrose 5%, IV: Lindner G, Funk GC. Hypernatremia in critically ill patients. J Crit Care. 2013
Apr;28(2):216.e11-20. http://www.ncbi.nlm.nih.gov/pubmed/22762930
viii
Furosemide, oral: Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.
Review. http://www.ncbi.nlm.nih.gov/pubmed/10824078
ix
Sodium chloride, 0.9%, IV: Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):15819. Review. http://www.ncbi.nlm.nih.gov/pubmed/10824078
x
Praziquantel: PHC STGs and EML, 2014. http://health.gov.za/
xi
Ciprofloxacin, oral: PHC STGs and EML, 2014. http://health.gov.za/
Ciprofloxacin, oral: Lewis DA, Gumede LY, van der Hoven LA, de Gita GN, de Kock EJ, de Lange T, Maseko V,
Kekana V, Smuts FP, Perovic O. Antimicrobial susceptibility of organisms causing community-acquired urinary
tract infections in Gauteng Province, South Africa. S Afr Med J. 2013 Mar 15;103(6):377-81.
http://www.ncbi.nlm.nih.gov/pubmed/23725955
xii
Fosfomycin, oral: Falagas ME, Vouloumanou EK, Togias AG, Karadima M, Kapaskelis AM, Rafailidis PI,
Athanasiou S. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized
controlled trials. J Antimicrob Chemother. 2010 Sep;65(9):1862-77. http://www.ncbi.nlm.nih.gov/pubmed/20587612
Fosfomycin, oral: Lewis DA, Gumede LY, van der Hoven LA, de Gita GN, de Kock EJ, de Lange T, Maseko V,
Kekana V, Smuts FP, Perovic O. Antimicrobial susceptibility of organisms causing community-acquired urinary
tract infections in Gauteng Province, South Africa. S Afr Med J. 2013 Mar 15;103(6):377-81.
http://www.ncbi.nlm.nih.gov/pubmed/23725955
xiii
Nitrofurantoin: SAMF, 2014.
xiv
Ceftriaxone, IM: PHC STGs and EML, 2014. http://health.gov.za/
Ceftriaxone, IM: Newman LM, Moran JS, Workowski KA. Update on the management of gonorrhea in adults in
the United States. Clin Infect Dis. 2007 Apr 1;44Suppl 3:S84-101.Review.
http://www.ncbi.nlm.nih.gov/pubmed/17342672
Ceftriaxone, IM: Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2010.MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1-110. Erratum in:
MMWR Recomm Rep. 2011 Jan 14;60(1):18. Dosage error in article text. http://www.cdc.gov/std/treatment/2010/
xv
Azithromycin, oral: PHC STGs and EML, 2014. http://health.gov.za/
Azithromycin, oral: Azithromycin: Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial
infections: a meta-analysis of randomized clinical trials. Sex Transm Dis. 2002 Sep;29(9):497-502.
http://www.ncbi.nlm.nih.gov/pubmed/12218839
xvi
Alpha-blocker (e.g. tamsulosin): Djavan B, Marberger M. A meta-analysis on the efficacy and tolerability of
alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic
obstruction. Eur Urol. 1999;36(1):1-13. http://www.ncbi.nlm.nih.gov/pubmed/10364649
xvii
NSAID, oral: Afshar K, Jafari S, Marks AJ, Eftekhari A, MacNeily AE. Nonsteroidal anti-inflammatory drugs
(NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev. 2015 Jun 29;6:CD006027.
http://www.ncbi.nlm.nih.gov/pubmed/26120804
2015
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8.1 ACROMEGALY
E22.0
DESCRIPTION
Acromegaly is a disorder caused by growth hormone (GH) hypersecretion
usually due to a pituitary adenoma, with associated morbidities, and
increased mortality.
This condition should be managed at a tertiary centre.
Transsphenoidal adenomectomy is the accepted form of primary therapy.
Radiotherapy post operatively may be required. In addition, adjunctive
medical therapy may be required in specific circumstances.
Investigations
If the diagnosis is suspected, screening should be done in consultation with
a specialist.
REFERRAL
All patients with suspected acromegaly to a hospital with endocrine and
neurosurgery facilities.
8.2 ADRENAL INSUFFICIENCY (ADDISON DISEASE)
E27.1
DESCRIPTION
Primary adrenocortical insufficiency.
Clinical presentation
Acute crisis: (not all symptoms and signs may occur in a particular patient,
so a high index of suspicion is needed).
» Hypotension
» depressed mentation
» fever
» hypoglycaemia
» GIT disturbances
» hyponatremia
» dehydration
» hyperkalaemia
» weakness
» acidosis
Chronic:
» hyperpigmentation
» GIT disturbances
» weakness and fatigue
» hypotension
» loss of weight
» hypoglycaemia
» postural dizziness
» hyponatraemia
» arthralgia
» hyperkalaemia
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8.1
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Always consider this diagnosis in a thin, hypotensive, hypoglycaemic patient,
or during stress e.g. sepsis. The combination of hyponatraemia and
hyperkalaemia should suggest possible primary adrenal insufficiency.
Investigations
08h00 serum cortisol level (or at time of presentation in acute crisis):
 550 nmol/L: virtually excludes the diagnosis
 < 100 nmol/L: highly suggestive of hypoadrenalism
 100–550
nmol/L
is
indeterminate
and may require
adrenocorticotropic hormone (ACTH) stimulation test:

ACTH depot, IM, 1 mg with blood sampling at 60 minutes.
o Post ACTH, serum cortisol level normal value: > 550 nmol/L or
double the pre-test level.
an
GENERAL MEASURES
All patients should wear a notification bracelet.
Consider sepsis and investigate for other causes.
MEDICINE TREATMENT
Acute crisis
Before administering hydrocortisone, ensure blood samples are taken for
serum cortisol and plasma ACTH, if feasible.

Hydrocortisone, IV, 200 mg 6 hourly.
o Change to oral maintenance therapy once stable.
LoE:III
To maintain adequate intravascular volume guided by blood pressure:

Sodium chloride 0.9%, IV with regular glucose monitoring, and 50%
dextrose boluses if required.
o Beware of fluid overload if the combination of sodium chloride
0.9%/dextrose 5% is utilised.
i
o The fluid deficit is often several litres.
LoE:III
Monitor glucose levels closely and treat hypoglycaemia if present.
Chronic
As maintenance therapy:
 Hydrocortisone, oral.
o Start with 10 mg in the morning and 5 mg at night.
o Increase the dose according to clinical response up to 20 mg in the
morning and 10 mg at night.
o In patients requiring a midday dose, a suggested regimen is 10 mg
in the morning, 5 mg at midday and 5 mg in the early evening.
OR
LoE:III

Prednisone, oral.
o Start with 5 mg daily.
o Increase to maximum of 7.5 mg daily, if necessary.
2015
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ENDOCRINE SYSTEM
For patients who have symptoms of mineralocorticoid deficiency:

Fludrocortisone, oral, 50–100 mcg daily may be required to normalise
the potassium and to reduce postural hypotension in primary
hypoadrenalism.
o Titrate dose of fludrocortisone in consultation with a specialist.
ii
LoE:III
Monitor response to therapy with:
» Symptoms: improvement in fatigue and GIT disturbances.
» Blood pressure: normotensive and no postural drop.
» Electrolytes: normal Na+ and K+.
During times of severe “stress” i.e. acute illness, surgery, trauma, etc.:

Hydrocortisone, IV, 100 mg 6 hourly.
With minor stress maintenance therapy should be doubled for the duration of
illness and gradually tapered to usual dose.
REFERRAL
All suspected cases, for full evaluation.
8.3 ANDROGEN DEFICIENCY
E29.1
DESCRIPTION
Reduced testosterone due to hypothalamic/pituitary hypofunction or primary
testicular failure.
Investigations
» Morning (08h00–09h00) serum total testosterone.
» LH and FSH
Serum testosterone
Primary testicular failure
Below normal
Secondary
Below normal
(hypothalamic/pituitary)
hypogonadism
LH and FSH
Above normal
Normal or below
normal
Note: If the serum total testosterone concentration is borderline low repeat
the test before replacement therapy is initiated.
» Prolactin
» Sperm count, if infertility is a consideration.
» Further investigations to determine cause to be undertaken after referral;
consult a specialist.
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8.3
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MEDICINE TREATMENT
Screen hypogonadal men for prostate cancer before beginning
testosterone replacement. Testosterone therapy can induce prostatic
hypertrophy, polycythaemia, liver dysfunction, sleep apnoea and
hyperlipidaemia. Baseline investigations for these are required prior to
initiation of therapy and long-term surveillance is required.
Individualise dosage and review doses based on clinical response.

Testosterone cypionate, deep IM, 200–300 mg every 2–4 weeks.
LoE:III
Monitor patients for prostate cancer during treatment.
8.4 CUSHING SYNDROME
E24.9
DESCRIPTION
Cushing syndrome is an illness resulting from excess cortisol secretion or
exogenous glucocorticoid administration. Cushing disease is hypercortisolism
secondary to an ACTH-secreting pituitary tumour.
Investigations
Screening tests for Cushing syndrome: 24 hour urinary free cortisol.
Low dose overnight dexamethasone (or when unavailable, betamethasone 1
mg equivalent to dexamethasone 1 mg) suppression test:

Dexamethasone, oral, 1 mg.
o Administer close to midnight.
o Measure plasma cortisol at 8 am, after breakfast.
o In normal people morning cortisol will be suppressed to <50 nmol/L.
o Refer if levels not suppressed.
iii
LoE:III
GENERAL MEASURES
Check for hypertension and diabetes and treat accordingly.
Check potassium.
REFERRAL
All cases for investigation of aetiology and appropriate management.
8.5 DIABETES MELLITUS
DESCRIPTION
Types of diabetes:
» Type 1
» Type 2
2015
8.4
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»
»
ENDOCRINE SYSTEM
Other specific types, including pancreatic diabetes mellitus.
Gestational diabetes mellitus – See Section 6.2: Diabetes Mellitus in
Pregnancy.
GENERAL MEASURES
All patients require lifestyle modification.
In patients with type 2 diabetes mellitus, weight loss if weight exceeds ideal
weight.
Correct meal/energy distribution.
Moderate or no alcohol intake.
Encourage smoking cessation.
Increased physical activity, aim for 30 minutes per day 5 times a week.
Education about foot care is essential.
Monitoring
At every visit:
» Inquire about:
- symptoms of hypoglycaemia, symptoms of microvascular and
macrovascular complications
- changes in medication
- changes in weight, physical activity, diet, smoking and alcohol
- mood and symptoms of depression
- impact of diabetes on occupation, driving
» Examination:
- blood glucose (finger prick)
- weight, height
- blood pressure and cardiovascular examination
- inspect insulin injection sites, if relevant
- inspect feet and look for signs of peripheral neuropathy
iv
LoE:III
Measure HbA1c:
» 6-monthly in patients who meet treatment goals, and
» 3-monthly in patients whose control is sub-optimal or if therapy has
changed, until stable.
Note: Monitoring of HbA1c implies that active clinical management will be
implemented if the level is sub-optimal.
v
LoE:III
Annually:
» Examination:
- Examine visual acuity and retinae with an ophthalmoscope or retinal
camera
- Examine the cardiovascular system for signs of macrovascular
disease.
- Examine for peripheral neuropathy.
» Laboratory tests:
- creatinine (including eGFR)
2015
8.5
CHAPTER 8
-
ENDOCRINE SYSTEM
spot urine albumin/creatinine ratio (microalbuminuria is defined as
2.5 to 25 mg/mmol in men, and 3.5 to 35 mg/mmol in women).
TARGETS FOR CONTROL
Glycaemic targets for control:
Patient type
-
Young, low risk
Newly diagnosed
No CVS disease
Majority of patients
Target
HbA1c
Target FPG*
Target PPG*
< 6.5%
4.0– 7.0 mmol/L
4.4– 7.8 mmol/L
< 7.0%
4.0– 7.0 mmol/L
5.0– 10.0 mmol/L
- Elderly
- High risk
< 7.5%
4.0– 7.0 mmol/L < 12.0 mmol/L
- Hypoglycaemic
unawareness
- Poor short-term
prognosis
*FPG: fasting plasma glucose; PPG: post prandial plasma glucose.
Non-glycaemic targets:
2.
- Body mass index ≤ 25 kg/m
- BP ≤ 140/80 mmHg and ≥ 120/70 mmHg.
In the elderly, the increased risk of hypoglycaemia must be weighed against
the potential benefit of reducing microvascular and macrovascular
complications.
In patients with severe target organ damage, therapy should be tailored on
an individual patient basis and should focus on avoiding hypoglycaemia.
REFERRAL
»
»
»
Inability to achieve optimal metabolic control.
Complications that cannot be managed on site, especially ophthalmic,
e.g. cataracts and proliferative retinopathy.
Recurrent severe hypoglycaemia.
8.5.1 TYPE 2 DIABETES MELLITUS
E11.9
Management includes:
» Treatment of hyperglycaemia.
» Treatment of hypertension and dyslipidaemia after risk-assessment.
See section 3.6: Hypertension.
» Prevention and treatment of microvascular complications.
2015
8.6
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»
ENDOCRINE SYSTEM
Prevention and treatment of macrovascular complications.
MEDICINE TREATMENT
Oral blood glucose lowering drugs
Metformin is the preferred initial medicine and is added to the combination of
dietary modifications and physical activity/exercise. If metformin, in maximal
dose, with diet and exercise fails to lower HbA 1c to target, a second agent
should be added. This second agent may be either a sulphonylurea, or basal
insulin. The specific indication is dependent on individual circumstances.
If a combination of two agents fails to lower HbA 1c to target, a third agent is
added. The preferential sequence of agents to use is metformin, followed by
the addition of sulphonylurea, followed by the addition of basal insulin.
The use of thiazolidinediones is not advised.
If the combination of two oral agents and basal insulin fails to lower HbA 1c to
target, or if other reasons to adjust therapy exist (such as nocturnal
hypoglycaemia), then intensified insulin therapy in consultation with a
specialist is required (either twice daily pre-mix, or basal-bolus therapy) and
sulphonylureas are discontinued.
Note: Secondary failure of oral agents occurs in about 5–10% of patients
annually.
Metformin
 Metformin, oral, 500 mg twice daily with meals.
o Titrate dose slowly depending on HbA1c and/or fasting blood
glucose levels to a maximum dose of 850 mg 8 hourly.
vi
o Monitor renal function.
LoE:I
o Dose-adjust in renal impairment as follows:
- eGFR > 60 mL/min:
Normal daily dose (see above).
- eGFR < 60 mL/min:
Half of the daily dose.
- eGFR < 30 mL/min:
Stop metformin.
o Contra-indicated in:
vii
- renal impairment i.e. eGFR < 30 mL/min,
LoE:III
- uncontrolled congestive cardiac failure,
- severe liver disease,
- patients with significant respiratory compromise, or
- peri-operative cases.
Sulphonylurea derivatives: glimepiride or glibenclamide.
 Glibenclamide, oral, 2.5 mg daily 30 minutes before breakfast.
o Titrate dose slowly depending on HbA 1c and/or fasting blood
glucose levels to 15 mg daily.
o When ≥7.5 mg per day is needed, divide the total daily dose into 2,
with the larger dose in the morning.
o Avoid in the elderly and patients with renal impairment (i.e. eGFR <
60 ml/min).
OR
2015
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
ENDOCRINE SYSTEM
Glimepiride, oral, 1 mg daily.
o Titrate the dose to a maximum of 4 mg daily.
viii
LoE:III
Oral agents should not be used in type 1 diabetes and used with caution in
liver and renal impairment.
Metformin should be dose adjusted in renal impairment.
Monitor serum creatinine and estimated eGFR in patients with kidney
disease. Three monthly in patients with renal impairment.
Insulin therapy in type 2 diabetes
Indications for insulin therapy:
» Inability to control blood glucose with oral drugs,
combination/substitution insulin therapy.
» Temporary use for major stress, e.g. surgery, medical illness.
» Severe kidney or liver disease.
» Pregnancy.
i.e.
Note:
» At initiation of insulin therapy, give appropriate advice on self-blood
glucose monitoring (SBGM) and diet.
» It is advisable to maintain all patients on metformin once therapy with
insulin has been initiated.
Insulin type
Add on therapy:
 Neutral
Protamine
Hagedorn
(NPH) /
isophane
insulin
Substitution
therapy:
 Biphasic insulin
(30/70 mix)
Starting dose
8 units, (or 0.3 units per
kg body weight), in the
evening before
bedtime, but not after
22h00.
Increment
If the starting dose is
not effective increase
by 2-4 units per dose
every 3 to 7 days until
fasting glucose is in the
target range.
Max.daily dose
Refer if
recurrent
hypoglycaemia
occurs and
targets for
control are not
met.
Total daily dose: 15
units divided as follows:
 2/3 of total daily
dose, i.e. 10 units, 30
minutes before
breakfast.
 1/3 of total daily
dose, i.e. 5 units, 30
minutes before supper.
4 units weekly.
Refer if
recurrent
hypoglycaemia
occurs and
targets for
control are not
met.
Basal bolus insulin Start with 0.4 to 0.6
therapy
units per kg body
weight and divide this
total daily dose into
50% basal and 50%
bolus, using equal premeal doses
2015
First increment is
added to dose before
breakfast
Second increment is
added to dose before
supper.
Basal insulin is
adjusted according to
fasting glucose levels
and bolus insulin is
adjusted according to
pre- and post-meal
glucose, using the
patient’s home glucose
record as a guide.
Refer if
recurrent
hypoglycaemia
occurs and
targets for
control are not
met.
8.8
CHAPTER 8
ENDOCRINE SYSTEM
Also see insulin protocols as in section 8.5.2: Type 1 diabetes mellitus.
ix
LoE:III
Note: Insulin requirements decrease in patients with chronic renal
impairment. In these situations, blood glucose monitoring must be done
regularly (at least daily) in order to reduce the dose appropriately, reducing
the risk of hypoglycaemia.
To reduce cardiovascular risk
All patients > 40 years of age:

HMGCoA reductase inhibitors (statins), e.g.:

Simvastatin, oral, 10 mg daily.
In patients < 40 years, risk assess for dyslipidaemia. See section 8.8:
Dyslipidaemia.
Aspirin therapy:
Use in adult Type 1 and Type 2 diabetic patients; only with a history of
cardiovascular disease i.e.
- ischaemic heart disease
- peripheral vascular disease
- previous thrombotic stroke
 Aspirin, orally, 150 mg daily.
x
LoE:I
Renal impairment
If urine albumin:creatinine ratio is > 2.5 mg/mmoL (men) or > 3.5 mg/mmoL
(women), add ACE-inhibitor, e.g.:
 Enalapril, oral, 5 mg 12 hourly, increasing to 10 mg 12 hourly depending
on blood pressure and albumin: creatinine ratio
xi
See section 7.1.1: Chronic Kidney Disease (CKD).
LoE:I
8.5.2 TYPE 1 DIABETES MELLITUS
E10.9
Management includes:
» Maintenance of glycaemic control within acceptable limits.
» Prevention of chronic complications.
» Prevention of acute complications, e.g. hyperglycaemic and hypoglycaemic
coma.
Insulin protocols
 Insulin, short acting SC, three times daily, 30 minutes before meals:
Regular human insulin.
Onset of action: 30 minutes.
Peak action: 2–5 hours.
Duration of action: 5–8 hours.
 Insulin, intermediate acting, SC, once or twice daily, usually at night, not
later than 10pm.
Neutral Protamine Hagedorn (NPH) insulin.
2015
8.9
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
ENDOCRINE SYSTEM
Onset of action: 1–3 hours.
Peak action: 6–12 hours.
Duration of action: 16–24 hours.
Insulin, biphasic, SC, once or twice daily.
Mixtures of regular human insulin and NPH insulin in different
30
proportions, e.g. /70.
Onset of action: 30 minutes.
Peak action: 2–12 hours.
Duration of action: 16–24 hours.
Selection of insulin
Basal bolus regimen
All type 1 diabetics should preferentially be managed with combined
intermediate-acting (basal) and short-acting insulin (bolus), the so-called
basal bolus regimen. This consists of pre-meal short-acting insulin and
bedtime intermediate-acting insulin not later than 22h00.
Insulin doses
The initial total daily insulin dose:
o 0.6 units/kg body weight.
The total dose is divided into:
o 40–50% basal insulin
o the rest of the total daily dose (TDD) is given as bolus insulin split
equally before each meal.
Adjust dose on an individual basis.
Twice daily Insulin
Twice daily pre-mixed insulin, i.e. a mixture of intermediate- or short- acting
insulin provides adequate control, when used with at least daily blood
glucose monitoring. It is a practical option for patients who cannot monitor
blood glucose frequently.
Insulin delivery devices
In visually impaired patients prefilled syringes should be used.
Home glucose monitoring
Patients on basal/bolus insulin should measure glucose at least twice daily
This may be individualised depending on the clinical need of the patient.
All patients with type 2 diabetes, on insulin, should be given test strips for
home glucose monitoring appropriate for their care plan.
It is important to maximise the value of home glucose monitoring by careful
review of home glucose records at each visit and appropriate patient
education in terms of self dose adjustment.
xii
LoE:I
2015
8.10
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ENDOCRINE SYSTEM
Glucagon
Type 1 diabetics, who are found to be at high risk of hypoglycaemia because
of recurrent episodes, should have a glucagon hypoglycaemia kit and both
the patient and their family should be trained to use this emergency therapy.
Repeat prescriptions of glucagon hypoglycaemia kit should only be given if
the kit has expired or been utilised.
LoE:III
8.6 DIABETIC EMERGENCIES
8.6.1 HYPOGLYCAEMIA
E10.64/E11.65
Diagnosis: Clinical
Symptoms:
» Anxiety
» Palpitations
» Headaches
Signs:
» Sweating
» Tachycardia
» Bizarre neurological signs
» Coma
»
»
»
Sweating
Hunger
Behavioural changes
»
»
»
Tremor
Confusion
Seizures
Biochemical
Act on finger prick blood glucose. Confirm with laboratory measurements if
uncertain.
TREATMENT
Start immediately.
At home:
Oral sugary drinks or paste, if able to swallow. Initially 15 g of quick-acting
oral carbohydrate should be administered and the glucose response
checked in 15-20 minutes; the treatment should be repeated if finger-prick
glucose fails to increase. If the episode is severe, family members should
administer glucagon.
In hospital:
 Dextrose 50%, rapid IV injection, 50 mL.
Assess clinical status and finger prick glucose level over the next 5–10 minutes.
xiii
LoE:III
Establish a large bore intravenous line and keep open with:
 Dextrose 10%, IV.
2015
8.11
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ENDOCRINE SYSTEM
If no clinical response, give a second injection of:
 Dextrose 50%, IV, 50 mL.
To prevent recurrent hypoglycaemia, continue infusion with:
 Dextrose 10%, IV infusion, at a rate of ± 1 L 6 hourly.
Once blood glucose is normal or elevated, and the patient is awake, check blood
glucose hourly for several hours, and check serum potassium for hypokalaemia.
If intravenous glucose cannot be given, for any reason, give:
 Glucagon, IM, 1 mg.
o Blood glucose will take 10–15 minutes to rise.
o May cause nausea and vomiting.
If the patient has not regained consciousness after 30 minutes with normal
or elevated blood glucose, look for other causes of coma.
Once the patient is awake, give a snack if possible, and admit for
observation and education etc., to prevent further hypoglycaemic episodes.
If hypoglycaemia was caused by a sulphonylurea, the patient will require
hospitalisation and a prolonged intravenous glucose infusion.
Observe patient for at least 12 hours after glucose infusion has stopped.
Recurrent hypoglycaemia
In cases of recurrent hypoglycaemia consider:
» inappropriate management, e.g. too much insulin or too high dose of
sulphonylurea,
» poor meal adherence
» poor adherence,
» alcohol abuse,
» factitious administration of insulin,
» the “honeymoon” period of type 1 diabetes,
» the advent of renal failure,
» hypoglycaemic unawareness, or
» pancreatic diabetes/malabsorption.
Other causes of hypoglycaemia should also be considered e.g. associated
Addison’s disease or hypopituitarism.
Recurrent hypoglycaemia may be the cause of hypoglycaemic unawareness,
which may occur in patients with type 1 diabetes. The loss of warning
symptoms can lead to severe hypoglycaemia. In some cases this situation can
be restored to normal with avoidance of any hypoglycaemia for at least 2–4
weeks.
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ENDOCRINE SYSTEM
8.6.2 DIABETIC KETOACIDOSIS (DKA) AND
HYPEROSMOLAR HYPERGLYCAEMIC STATE (HHS)
E10.0
Diabetic comas – recognition and clinical profiles
DKA often occurs in younger patients and develops over hours to days.
There may be vomiting, abdominal pain and acidotic breathing.
» blood glucose usually < 40 mmol/L
» blood ketones are positive
» serum osmolality < 350 mOsm/L.
Hyperosmolar hyperglycaemic state (HHS) is a syndrome characterised by
impaired consciousness, sometimes accompanied by seizures, extreme
dehydration and severe hyperglycaemia, that is not accompanied by severe
ketoacidosis (pH usually >7.2). It usually occurs in the elderly type 2 diabetic
and develops over days to weeks.
» Blood glucose usually > 40 mmol/L.
» Blood ketones usually negative to moderately elevated.
» Urine ketones may be positive.
» Serum osmolality is > 320 mOsm/L.
Anion gap = Na – (CI + HCO3) (Normal = ± 12 : DKA > 20)
Calculated serum osmolarity = 2 (Na + K) + glucose + urea.
GENERAL MEASURES
All patients:
» Set up an intravenous line.
» Protect airway and insert a nasogastric tube, if unconscious.
» Monitor urine output.
» Monitor plasma glucose, ketones, urine and electrolytes and venous
blood gas.
» Look for precipitating causes, e.g. infection and MI.
MEDICINE TREATMENT
Fluids
Average deficit 6 L, may be as much as 12 L.
If renal or cardiac disease is present, monitor with central venous pressure.
In the absence of renal or cardiac compromise:

Sodium chloride 0.9%, IV, 15–20 mL/kg in the first hour.
st
o Patients <20 years of age: initial volume of 10–20 mL/kg in the 1 hour.
o Subsequent infusion rate varies from 5–15 mL/kg/hour depending
on the clinical condition.
o Correction of estimated deficits should take place over 24 hours.
o The volume infused in the first 4 hours should not exceed 50 mL/kg.
o Fluid therapy thereafter is calculated to replace the estimated deficit
in 48 hours, ± 5 mL/kg/hour.
o Reduction in serum osmolality should not exceed 3 mOsm/kg/hour.
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ENDOCRINE SYSTEM
Correct plasma sodium value for blood glucose.
[Rough guide: divide glucose by 3 and add to sodium value.]
+
If plasma Na > 140 mmol/L:
 Sodium chloride 0.45%, IV.
+
If plasma Na < 140 mmol/L:
 Sodium chloride 0.9%, IV.
If plasma glucose < 15 mmol/L, but ketones still present:
 Dextrose 5% or dextrose 5% in sodium chloride 0.9%, IV.
xiv
LoE:III
Note:
» Adjust fluid volumes according to clinical criteria.
» Cerebral oedema may occur with over-aggressive fluid replacement or
rapid sodium change.
Potassium
Potassium will fall on insulin treatment and patients with DKA have
potassium depletion even if initial potassium is normal or high.
It is therefore essential to monitor and replace potassium.
Total body deficit 300–1 000 mmol.
(1 ampoule = 20 mmol = 10 mL)

Potassium chloride, IV, added to 1 L of fluid.
o potassium < 3.5 mmol/L:
add 40 mmol (2 ampoules)
o potassium 3.5–5.5 mmol/L:
add 20 mmol (1 ampoule)
o potassium > 5.5 mmol/L:
do not add any potassium
Maximum potassium dose: 40 mmol/hour.
Monitor potassium hourly initially, then 2 hourly when stabilised.
LoE:III
If serum potassium results are not readily available:
 Potassium chloride, IV, 20 mmol (1 ampoule) added to 1 L of fluid as
soon as the patient has established adequate urinary output.
Bicarbonate
There is no proven role for the use of intravenous sodium bicarbonate and it
could potentially cause harm.
Insulin therapy
Patients should be preferentially managed with continuous intravenous
infusions or hourly intramuscular injections (see below) in a high care ward,
with appropriate monitoring.
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ENDOCRINE SYSTEM
Note:
» Ketonaemia takes longer to clear than hyperglycaemia and combined
insulin and glucose (and K+) are needed to ensure clearance of
ketonaemia.
» Avoid focusing on glucose control alone!
» Continue insulin until acidosis and ketosis have resolved.
Continuous intravenous infusion:
 Insulin, short-acting, IV infusion, 50 units in 200 mL sodium chloride
0.9%.
o 4 mL solution = 1 unit insulin.
o Initial infusion: 0.1 unit/kg/hour.
o Usually 5–7 units/hour: 20–28 mL/hour.
st
o If plasma glucose does not fall by 3 mmol/L in the 1 hour, double
the insulin infusion (hourly) until a steady reduction of plasma
glucose is achieved, i.e. at least 3–4 mmol/L per hour.
o If plasma glucose < 14 mmol/L, reduce insulin infusion rate to 1-2
units/hour and adjust subsequently according to hourly bedside
capillary glucose level measured with glucose test strips.
Hourly intramuscular bolus injections:
Where intravenous infusion cannot be safely administered:

Insulin, short acting
o Dilute 100 units with sodium chloride 0.9% to 10 mL i.e. 10
units/mL.
o Loading dose: 0.5 units/kg body weight.
o Administer half the dose as an intravenous bolus injection and the
other half IM. Do not administer with an insulin syringe and needle.
o Subsequent hourly doses: ± 5–10 units IM every hour (i.e. 0.1
units/kg/hour) and titrated against the bedside capillary glucose level.
Progress management
Continue insulin therapy until the acidosis has resolved and:
o the patient is able to eat, and
o subcutaneous insulin therapy is instituted either at previous doses or, for
newly diagnosed diabetes at 0.5–1 unit/kg total daily dose divided into at
least 2 doses with mixed short and long acting insulin (biphasic insulin
2
1
/3 in the morning and /3 at night).
Infusion must overlap with subcutaneous regimen for 1–2 hour to avoid
reversion to keto-acidosis.
Heparin.
For all patients:
 Unfractionated heparin, SC, 5 000 units 12 hourly.
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OR

Low molecular weight heparin, e.g.:
Enoxaparin, SC, 40 mg daily.
ENDOCRINE SYSTEM
xv
LoE:I
8.7 COMPLICATIONS OF DIABETES
Macrovascular complications
Diabetic patients with a history of myocardial infarction, vascular bypass,
stroke or transient ischemic attack, peripheral vascular disease, claudication,
or angina need secondary prevention with aspirin and a statin – see section
3.1 Ischaemic heart disease and atherosclerosis, prevention
Hypertension
See section 3.6: Hypertension.
Dyslipidaemia
See section 8.8: Dyslipidaemia.
8.7.1 DIABETIC NEUROPATHIES
Type 1:E10.4/Type2:E11.4
DESCRIPTION
Neuropathies are a common complication of diabetes. They play an
important role in the morbidity and mortality suffered by people with
diabetes.
There are three major categories:
» peripheral neuropathy,
» autonomic neuropathy, and
» acute onset neuropathies.
MEDICINE TREATMENT
Ensure appropriate glycaemic control.
Exclude or treat other contributory factors e.g.:
» alcohol excess,
» vitamin B12 deficiency, if suspected,
» uraemia, and
» HIV infection.
Pain
 Amitriptyline, oral, 10–25 mg at night increasing to 100 mg, if necessary.
AND/OR

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
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ENDOCRINE SYSTEM
If ineffective consider adding:
 Carbamazepine, oral, 100 mg daily.
o Increase dose to 200 mg 12 hourly, if necessary.
o Maximum dose: 1200 mg daily.
Gastroparesis
 Metoclopramide, oral, 10 mg 8 hourly, 30 minutes before meals.
If ineffective consult a specialist.
8.7.2 DIABETIC KIDNEY DISEASE
N18.9
See section 7.1.1: Chronic Kidney Disease (CKD).
8.7.3 DIABETIC FOOT ULCERS
L97
GENERAL MEASURES
Metabolic control.
Treat underlying comorbidity.
Relieve pressure: non-weight bearing is essential.
Smoking cessation is essential.
Deep (limb-threatening) infection
CXR of affected limb.
Surgical drainage as soon as possible with removal of necrotic or poorly
vascularised tissue, including infected bone – refer urgently.
Revascularisation, if necessary
Local wound care
Frequent wound debridement with scalpel, e.g. once a week.
Frequent wound inspection.
Absorbent, non-adhesive, non-occlusive dressings.
MEDICINE TREATMENT
Superficial ulcer with extensive infection
Debridement with removal of all necrotic tissue.
Antibiotic therapy
For polymicrobial infection:

Topical antibiotics are not indicated.

2015
Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 10 days.
o Longer course of therapy may be necessary.
8.17
CHAPTER 8
ENDOCRINE SYSTEM
Severe infection

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly.
Severe penicillin allergy

Clindamycin, oral, 150 mg 8 hourly.
AND

Gentamicin, IV, 6 mg/kg daily
REFERRAL
Arterial revascularisation procedures.
8.8 DYSLIPIDAEMIA
E78.9
DESCRIPTION
Non-pharmacological therapy plays a vital role in the management of
dyslipidaemia. Many patients with mild or moderate dyslipidaemia will be
able to achieve optimum lipid levels with lifestyle modification alone and may
not require lifelong lipid modifying therapy.
Accompanying modifiable risk factors for coronary artery disease (CAD) e.g.
hypertension, smoking, diabetes, must be sought and treated.
Underlying causes of secondary dyslipidaemia, e.g. excess alcohol intake,
hypothyroidism, should be identified and corrected.
The goal of treatment should be explained clearly to the patient and the risks
of untreated dyslipidaemia should be emphasised.
GENERAL MEASURES
Lifestyle modification
Dietary strategies are effective.
» Replace saturated fats with unsaturated fats (mono-and polyunsaturated
fats) without increasing calories from fats.
» Consume a diet high in fruits, vegetables, nuts and whole unrefined
grains.
Smoking cessation.
Increase physical activity.
Maintain ideal body weight.
MEDICINE TREATMENT
Indication for medicine therapy
Cardiovascular
The main indication for lipid-modifying medication is to reduce the risk of a
cardiovascular event. Medicine therapy should be considered when nonpharmacological means have failed to reduce the lipid levels to within the
target range. When lipid-lowering medicines are used, this is always in
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ENDOCRINE SYSTEM
conjunction with ongoing lifestyle modification.
Patients with clinically manifest vascular disease require lipid-lowering
medicine therapy with a HMGCoA reductase inhibitor, irrespective of
cholesterol levels:
» confirmed ischaemic heart disease,
» peripheral vascular disease,
» atherothrombotic stroke, and
» type 2 diabetics > 40 years of age.
Such high-risk patients will benefit from lipid lowering (statin) therapy
irrespective of their baseline LDL-C levels.
Patients without established vascular disease, with a risk of MI of greater
than 20% in 10 years, and who have not achieved lipid goals within 3
months of dietary management – (See section 3.1: Ischaemic heart disease
and atherosclerosis, prevention).
Non-cardiovascular
The most serious non-cardiovascular complication of dyslipidaemia is the
development of acute pancreatitis. This is seen in patients with severe
hypertriglyceridaemia (fasting triglycerides >10 mmol/L). Ideally such
patients should be discussed with a lipid specialist.
Fibrates are the medicines of choice for severe hypertriglyceridaemia, not
due to secondary causes.
Choice of medication
Depends on the type of lipid disturbance:
» predominant hypercholesterolaemia:
» mixed hyperlipidaemia:
» predominant hypertriglyceridaemia:


statin
statin or fibrate
fibrate
HMGCoA reductase inhibitors (statins) that lowers LDL by at least 25%,
e.g.:
Simvastatin, oral, 10 mg daily.
OR
For patients with moderate to severe fasting hypertriglyceridaemia and for
patients on ARV therapy i.e. triglycerides > 10 mmol/L:

Fibric acid derivatives e.g.:

Bezafibrate, oral, 400 mg daily.
Dyslipidaemia in HIV infected patients: See section 10.1.1: Management of
selected antiretroviral adverse drug reactions.
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REFERRAL
»
»
Patients with possible familial hypercholesterolaemia (FH) i.e. random
cholesterol >7.5 mmol/L or with tendon xanthomata (See section 3.1:
Ischaemic heart disease and atherosclerosis).
Suspected severe familial dyslipidaemias.
8.9 HYPERCALCAEMIA, INCLUDING PRIMARY
HYPERPARATHYROIDISM
E83.50/E21.0
DESCRIPTION
When serum calcium (corrected for albumin) concentrations exceed the
upper limit of normal.
Aetiology
» Ambulatory patients: most common cause is hyperparathyroidism
(>90% of cases).
» Hospitalised patients: malignancies are the most common cause (65%
of cases). Hyperparathyroidism accounts for another 25%.
» Granulomatous disease (e.g. sarcoid).
» Immobilisation in those with high bone turnover.
Investigations
Draw blood for parathyroid hormone (PTH) and simultaneous calcium,
phosphate, magnesium, albumin, creatinine and sodium and potassium and
25 hydroxy-vitamin D concentrations.
A detectable PTH in the presence of hypercalcaemia indicates PTHdependent hyperparathyroidism.
MEDICINE TREATMENT
Hypercalcaemia
Patients with moderate/severe hypercalcaemia should be kept well hydrated
and may need several litres of fluid.
Avoid thiazide diuretics as they increase serum calcium concentration.
The addition of furosemide has not been shown to be of benefit.
For symptomatic hypercalcaemia:

Sodium chloride solution 0.9%, IV infusion, 4–6 L in 24 hours.
o Monitor urine output.
If still symptomatic after 24 hours and adequate hydration, or if initial serum
calcium is > 3 mmol/L:
ADD

Pamidronic acid, IV infusion, 30 mg over 4 hours according to plasma
calcium concentration (specialist initiated).
o Dilute each 15 mg in 125 mL sodium chloride solution 0.9% and
2015
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o
o
ENDOCRINE SYSTEM
administer over 1 hour.
Doses should not be repeated until after 7 days.
A response is noted within 48 hours and trough
reached in 5–7 days.
xvi
LoE:II
In patients with granulomatous disease and haematological malignancies:
 Prednisone, oral, 40 mg depending on response, daily.
LoE:III
REFERRAL
When a diagnosis of hyperparathyroidism is confirmed or other cause is not
obvious.
8.10 HYPOCALCAEMIA
E83.5
DESCRIPTION
Serum calcium (corrected for albumin) below the lower limit of normal.
Causes
» Renal failure.
» Hypoparathyroidism:
post neck surgery,
radiotherapy, or
idiopathic.
» Vitamin D related, (deficient intake, activation or action).
» Hypomagnesaemia.
» Malabsorption syndrome.
MEDICINE TREATMENT
Therapy is aimed at treating the underlying cause.
For acute hypocalcaemia with neurological problems:

Calcium gluconate 10%, IV, 10 mL given over 15–30 minutes, with ECG
monitoring.
o This may be repeated.
AND/OR

Calcium gluconate 10%, 20–30 mL in 1 L dextrose 5% and given over
12–24 hours.
LoE:III
For hypoparathyroidism:

Calcium, elemental, oral, 500–1 500 mg daily in divided doses.
AND

Alfacalcidol, oral, 1–3 mcg daily.
Correct magnesium deficiency if present.
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Renal failure:
See Section: 7.1.1 Chronic Kidney Disease (CKD).
REFERRAL
»
»
If cause is uncertain.
If hypoparathyroidism suspected and PTH analysis required as above.
8.11 HYPOTHYROIDISM
E03.9
DESCRIPTION
Causes
Common causes of primary hypothyroidism are:
» chronic autoimmune thyroiditis,
» post surgery, and
» post radio-active iodine.
Secondary hypothyroidism (less than 1% of cases) may be due to any cause
of anterior hypopituitarism.
Investigations
Thyroid stimulating hormone (TSH) and thyroxine (T4) initially. In primary
hypothyroidism TSH is elevated and T4 is low. If TSH is normal or slightly
elevated and T4 is low this suggests hypopituitarism: take blood for cortisol
and ACTH, give hydrocortisone replacement before starting levothyroxine
and investigate for causes of hypopituitarism.
MEDICINE TREATMENT

Levothyroxine, oral, 100 mcg (microgram) daily.
o If there is a risk of ischaemic heart disease, start at 25 mcg daily
and increase by 25 mcg every 4 weeks.
Check TSH and T4 after 2–3 months and adjust dose if required.
TSH levels will take several weeks to stabilise. Once stable check T 4 and
TSH annually.
Hypothyroidism in pregnancy
About 60% of hypothyroid pregnant women need an increase in
levothyroxine therapy in the second and third trimesters. Because T4 takes a
st
long time to reach steady state and 1 trimester hypothyroidism is
undesirable for the fetus, for patients with borderline control (TSH >1.2) it is
advisable to increase the pre-pregnancy dose by 30%. Check TSH monthly
and increase levothyroxine doses to keep serum TSH levels low normal and
free T4 levels in the high-normal range. After delivery, revert to preconception doses.
Note: TSH reference range is trimester-specific.
xvii
LoE:II
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8.12 OSTEOPOROSIS
M81.9
DESCRIPTION
A disease characterised by low bone mass and micro-architectural bone
deterioration leading to bone fragility and increase in fracture risk.
GENERAL MEASURES
Prevention
Adequate energy and protein intake.
Adequate dietary calcium intake (>1 g/day) particularly in the young, in
breastfeeding mothers and in the elderly. This is preferably obtained from a
dietary source.
Weight bearing exercises, e.g. brisk 30 minute walk 3 times a week.
Smoking cessation.
Ensure alcohol intake is < 10 units /week.
Avoid falls.
MEDICINE TREATMENT
In the institutionalised frail elderly patients, supplementation with calcium
and vitamin D may reduce the incidence of hip fractures:
 Calcium, elemental, oral, 1 000 mg daily.
AND

Vitamin D, oral, 800 units daily.
Note: Routine supplementation with calcium and vitamin D marginally
increases the risk of myocardial infarction and stroke and is of unclear
xviii
benefit in other populations.
LoE:I
Secondary prevention of osteoporotic fracture, including patients on longterm corticosteroids:
In severe osteoporosis, i.e. patients who have a T-score of –2.5 (severe
osteoporosis) plus an osteoporotic fracture:
 Alendronate, oral, 10 mg daily for a maximum duration of 5 years.
This should be given with:
 Calcium, elemental, oral, 1 000 mg daily.
AND

Vitamin D, oral, 800 units daily.
Hormone replacement therapy
See Section 5.12: Menopause and Perimenopausal Syndrome.
Only indicated early in menopause, if vasomotor symptoms are significant.
Review contra-indications before initiating therapy.
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ENDOCRINE SYSTEM
REFERRAL
»
»
»
»
»
To establish diagnosis (bone densitometry).
For initial assessment.
Initiation and monitoring response to therapy and 18–24 monthly bone
mineral density (BMD).
Fractures suspected to be due to osteoporosis for consideration for
alendronate
Patients not tolerating oral alendronate.
8.13 OSTEOMALACIA/RICKETS
M83.9
DESCRIPTION
A disorder of mineralisation of newly synthesised bone matrix.
REFERRAL
All patients
8.14 PAGET’S DISEASE
M88.9
DESCRIPTION
Bone disease characterised by localised uncontrolled formation of highly
active osteoclasts leading to an increase in bone resorption followed by
chaotic increase in bone formation.
GENERAL MEASURES
Most cases are mild and asymptomatic and no treatment is required. The
diagnosis is supported by isolated high alkaline phosphatase and typical
CXR changes.
Avoid high calcium diet when immobile as hypercalcaemia may occur with
immobilisation.
Differentiate bone pain of Paget’s, especially at night, from arthritic pain in
joints near deformed bone, e.g. hip and knee joints, as well as pain resulting
from fracture or complicating osteosarcoma.
MEDICINE TREATMENT
For arthritic pain:

Ibuprofen, oral, 400 mg 8 hourly with meals.
REFERRAL
All patients.
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ENDOCRINE SYSTEM
8.15 PITUITARY DISORDERS
8.15.1 PROLACTINOMA
D35.2
DESCRIPTION
Prolactinoma is the most common functioning pituitary tumour.
Investigations
Serum prolactin, beta-HCG.
Note:
» There are numerous causes of hyperprolactinaemia other than a
prolactinoma, so secondary causes must be excluded e.g. pregnancy,
medicines, physiological, hypothyroidism, chronic renal failure and
tumours.
» In patients with prolactinoma, serum prolactin levels are usually
elevated ≥ 4 times the upper limit of the normal reference range for the
laboratory method used. Lesser degree of elevation of serum prolactin
may also be found in patients with other pituitary tumours associated
with pituitary stalk compression.
MEDICINE TREATMENT
Dopamine agonist therapy is the treatment of choice.

Bromocriptine, oral, 1.25 mg at bedtime with a snack.
o Initial maintenance dose: increase dose to 2.5 mg 12 hourly with
food and check prolactin 4 weeks later.
o Higher doses may be needed.
o GIT side effects are minimised by giving doses with food.
o If total dose of 10 mg does not normalise prolactin, refer.
REFERRAL
»
»
All tumours, once causes of secondary hyperprolactinaemia have been
sought and excluded.
Intolerance to bromocriptine.
Urgent
»
»
Visual disturbances suggesting compression of optic chiasm.
Pituitary apoplexy.
8.15.2 ANTERIOR HYPOPITUITARISM
E23.0
DESCRIPTION
Absent or diminished secretion of one or more anterior pituitary hormones
due to primary damage of the anterior pituitary gland or secondary to
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ENDOCRINE SYSTEM
hypothalamic dysfunction, which may result in hypothyroidism and/or
hypoadrenalism and/or hypogonadism or growth retardation in children.
GENERAL MEASURES
Surgery is required for large tumours, pituitary apoplexy, and hormone
secreting tumours (except for most patients with prolactinomas, who
generally respond well to medical therapy). Radiotherapy may be required in
selected patients
A notification bracelet is needed.
MEDICINE TREATMENT
Acute crisis
Treat as for acute crisis in section 8.2: Adrenal Insufficiency (Addison’s
Disease).
Chronic
See section 8.2: Adrenal Insufficiency (Addison’s Disease).
Hypoadrenalism
See section 8.2: Adrenal Insufficiency (Addison’s disease) and 8.11:
Hypothyroidism.
Hypothyroidism
See section 8.11: Hypothyroidism.
Hypogonadism
Individualise dosage and need for replacement according to age, symptoms, etc.
Women:
As for postmenopausal HT,
perimenopausal syndrome.
see
section
5.12:
Menopause
and
Men:
 Testosterone, IM, 200–300 mg every 3–4 weeks.
See section 8.3: Androgen deficiency.
REFERRAL
All diagnosed patients for initial assessment.
8.15.3 DIABETES INSIPIDUS (POSTERIOR
HYPOPITUITARISM)
E23.2
DESCRIPTION
Damage to the posterior pituitary leading to deficient production of
antidiuretic hormone. Characterised by the passage of large amounts of
dilute urine, usually > 2.5 litres daily.
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Causes include head trauma and neurosurgery but most cases are
idiopathic.
Consultation with a specialist is recommended.
GENERAL MEASURES
Rehydration with water or hypotonic fluids.
MEDICINE TREATMENT
Replacement therapy

Desmopression, oral, 0.2–1.2 mg daily.
o Optimal dose: 0.1–0.2 mg 8 hourly.
LoE:III
Acute management
Post operatively:

Desmopressin, nasal spray, 10–20 mcg (microgram) 12–24 hourly.
OR

Desmopressin, oral, 0.1 mg 8 hourly.
o Adjust dose according to response to a maximum of 1.2 mg per day
in divided doses.
o Larger doses can lead to water overload and hyponatraemia.
OR

Desmopressin, SC, 1 mcg every 12 to 24 hours.
LoE:III
REFERRAL
Water deprivation may be necessary to confirm the diagnosis. Careful
monitoring of electrolytes and exclusion of fluid overload while on therapy is
essential to determine the appropriate dose.
8.16 PHAEOCHROMOCYTOMA
C74.9
Description
Catecholamine-secreting tumour of the adrenal medulla.
Clinical presentation
Always consider in hypertensive patients who have paroxysmal symptoms:
» headaches,
» tremor,
» GIT symptoms,
» recurrent chest discomfort,
» palpitations,
» sweating, and
» anxiety.
There is marked inter-individual variation in symptoms.
Patients may also have orthostatic changes in BP.
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ENDOCRINE SYSTEM
Diagnosis
24 hour urine acidified with HCl: normetanephrine (NMA), vanillylmandelic
acid (VMA), should be ≥ twice normal for a definite diagnosis. Test is best
done during a paroxysm, if possible, using at least 2 samples.
There are many drugs, foods and diseases that can falsely elevate or lower
NMA/VMA levels; therefore the clinician must interpret the results in the light
of the clinical context and after having taken an accurate history.
Screen:
» young hypertensive patient;
» hypertensive patients with paroxysmal symptoms; and
» patients with:
- a labile BP,
- a family history of a phaeochromocytoma,
- neurofibromatosis, or
- radiologic evidence of an adrenal mass.
GENERAL MEASURES
Surgical removal of the tumour.
MEDICINE TREATMENT
Once diagnosis is confirmed, initiate medication with immediate referral.
 Alpha blockers, e.g.:

Doxazosin, oral, 4 mg daily.
o Dose increase above 8 mg daily to control blood pressure may be
required.
xix
LoE:III
 Calcium channel blockers may be added, e.g.:

Amlodipine, oral, 5–10 mg daily
Note:
» Patients should not be given diuretic therapy unless pulmonary oedema
is present.
» β-blockers must be used with extreme caution in the management of
phaechromocytoma.
REFERRAL
All patients.
8.17 PRIMARY ALDOSTERONISM
E26.0
DESCRIPTION
Increased aldosterone production usually due to an adrenal adenoma
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ENDOCRINE SYSTEM
(Conn's syndrome) or idiopathic bilateral adrenal hyperplasia (the majority of
cases).
Clinical
Suspect in a patient with resistant hypertension or hypertension with
hypokalaemia.
Diagnosis
Elevated serum aldosterone with a suppressed renin level or elevated
aldosterone/renin ratio.
ACE-inhibitors, angiotensin receptor blockers (ARBs), and diuretics can give
falsely elevated or lowered results. Stop all these drugs for a minimum of 2
weeks before testing. Stop spironolactone for 6 weeks before testing.
Because of limited specificity, a positive screening test result should be
followed by a confirmatory test. A negative random ratio test does not
necessarily exclude the diagnosis.
MEDICINE TREATMENT
Adrenal adenoma
Adrenalectomy.
Bilateral hyperplasia
Standard anti-hypertensive therapy, including spironolactone.

Spironolactone, oral, 100–200 mg daily.
REFERRAL
All patients to an endocrinologist or a hypertension centre for confirmation of
the diagnosis and further treatment.
8.18 HYPERTHYROIDISM
E05
DESCRIPTION
Most common cause of hyperthyroidism is Graves’ disease, which is an
autoimmune condition resulting from the presence of thyroid stimulating
autoantibodies. Other common causes are toxic single or multinodular goitre
and sub-acute thyroiditis.
Investigation
TSH and free T4.
If TSH suppressed and free T4 normal, request free T3.
The usual biochemical abnormalities are: low TSH, elevated free T4/3
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Once thyrotoxicosis is confirmed, if cause is uncertain request thyroid uptake
scan. If uptake is:
» Elevated or diffuse: Grave’s disease.
» Markedly decreased: Thyroiditis.
» Patchy uptake with areas of increased uptake: Toxic multinodular goitre.
REFERRAL
»
»
»
»
»
Consultation with a specialist is recommended in all cases.
For thyroid scan if necessary.
Thyroid-associated ophthalmopathy.
When radioactive iodine or surgery is contemplated.
If patient is pregnant.
8.18.1 GRAVES’ HYPERTHYROIDISM
E05.0
MEDICINE TREATMENT

Carbimazole, oral, 20–40 mg daily.
o Titrate dose according to thyroid hormone levels (T4).
o Duration of therapy: 12–18 months.
o Durations of therapy longer than 12 months must be in consultation
with a specialist.
ß–blockers
Used to counteract excessive sympathetic symptoms, e.g. palpitations.
Dose is titrated according to the heart rate.
Give for 2–6 weeks, together with carbimazole until T4 levels normalise.
 Atenolol, oral, 50 mg daily.
o Titrate according to symptom control up to 100 mg daily.
Radioactive iodine
In the setting of Graves’ disease radioactive iodine may be administered for
failed medical therapy and may be indicated for patients with coexistent
heart disease.
It is contraindicated during pregnancy and lactation and in active thyroid
associated ophthalmopathy, unless corticosteroid cover is given.
Surgery
Consider in the following situations: large thyroid causing obstructive
symptoms, failure of anti-thyroid medicine therapy, allergy to anti-thyroid
nd
therapy, 2 trimester of pregnancy and not responding to or allergic to antithyroid medication.
Monitoring
Patients with Graves’ disease who are treated with anti-thyroid drugs should
be monitored every 6–8 weeks using a serum T4. TSH may remain
suppressed for months. Once in remission, patients may be monitored less
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ENDOCRINE SYSTEM
frequently to determine signs and symptoms of recrudescence of
thyrotoxicosis.
Because there is a risk of neutropenia or agranulocytosis with carbimazole,
therapy should be temporarily stopped and a white cell count (with differential)
must be done in patients presenting with an infection or sore throat.
Patients requiring longer than 18 months of therapy with carbimazole,
require specialist input.
Post-radio-active iodine TSH and free T4 should be checked at 6 weeks, 3,
6, 9 and 12 months and annually thereafter until either hypothyroidism
occurs or patient remains euthyroid for ± 3–4 years. Although uncommon,
hypothyroidism can occur years later.
8.18.2 TOXIC MULTINODULAR GOITER
E05.2
MEDICINE TREATMENT
Radio-active iodine
Radioactive iodine is the treatment of choice. Medical therapy is indicated
initially for patients with underlying heart disease to achieve euthyroidism before
radio-active iodine. Surgery is restricted to patients with obstructive symptoms.
8.18.3 SINGLE TOXIC NODULES
E05.1
MEDICINE TREATMENT
Radioactive iodine
Smaller nodules are best managed with radio-active iodine while larger
nodules may require surgery.
ß–blockers
Used to counteract excessive sympathetic symptoms, e.g. palpitations.
Dose is titrated according to the heart rate.
Give for 2–4 weeks.
 Atenolol, oral, 50 mg daily.
o Titrate according to symptom control up to 100 mg daily.
8.18.4 THYROIDITIS
E06
Toxic phase lasts up to 3 months.
MEDICINE TREATMENT
ß–blockers
Used to counteract excessive sympathetic symptoms, e.g. palpitations.
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Dose is titrated according to the heart rate.
Give for 2–4 weeks.
 Atenolol, oral, 50 mg daily
o Titrate according to symptom control up to 100 mg daily.
For painful subacute thyroiditis (De Quervain’s):
 NSAIDs, e.g.:
 Ibuprofen, oral, 400 mg 8 hourly with meals.
AND
 Prednisone, oral, 40 mg daily. Specialist consultation.
8.18.5 THYROID CRISIS
E05.5
MEDICINE TREATMENT
IV fluids as indicated.

Carbimazole, oral, 30 mg 6 hourly.
o After 30 minutes follow with 10 drops of Lugol’s iodine in milk and
continue 8 hourly.
o Administer second dose of carbimazole and continue 6 hourly until
crisis is controlled.
xx
AND
LoE:III
 Atenolol, oral, 50 mg daily
o Titrate according to symptom control up to 100 mg daily.
LoE:III
If life-threatening:
ADD
 Hydrocortisone, IV, 100 mg 8 hourly.
Treat precipitating illness and infection. ICU admission is desirable.
References:
i
Sodium chloride 0.9%, IV: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA,
Distiller LA, Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane
DT, Levitt NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ,
Randeree HAR, Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA
Guideline for the Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
Dextrose 50%, IV: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA,
Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt
NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR,
Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
Sodium chloride 0.9%/ dextrose 5%, IV: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM,
Dave JA, Distiller LA, Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P,
Khutsoane DT, Levitt NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer
PJ, Randeree HAR, Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA
Guideline for the Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
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ii
Fludrocortisone, oral: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller
LA, Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT,
Levitt NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree
HAR, Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
iii
Dexamethasone, oral: Findling JW, Raff H, Aron DC. The low-dose dexamethasone suppression test: a
reevaluation in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2004 Mar;89(3):1222-6.
http://www.ncbi.nlm.nih.gov/pubmed/15001614
iv
Monitoring: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA, Ganie
YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt NS,
May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR,
Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
v
Monitoring HbA1c: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA,
Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt
NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR,
Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
vi
Metformin: Effect of intensive blood-glucose control with metformin on complications in overweight patients with
type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep
12;352(9131):854-65. Erratum in: Lancet 1998 Nov 7;352(9139):1558.
http://www.ncbi.nlm.nih.gov/pubmed/9742977
Metformin: SAMF, 2014.
vii
Metformin (renal impairment): Canadian Diabetes Association Clinical Practice Guidelines Expert Committee.
Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
in Canada. Can J Diabetes 2013;37(suppl 1):S1-S212.
http://guidelines.diabetes.ca/app_themes/cdacpg/resources/cpg_2013_full_en.pdf
Metformin (renal impairment): NICE Clinical Guideline 87: Type 2 diabetes - The management of type 2
diabetes, 2009, 2014. [Online][Accessed 2014] Available at: www.nice.org.uk/Guidance/CG87
Metformin (renal impairment): Aronoff, Bennett et al. Drug Prescribing in Renal Failure: Dosing Guidelines for
Adults and Children, 5th Edition. American College of Physicians. United States of America, 2007.
Metformin (renal impairment): Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to
moderate renal insufficiency. Diabetes Care. 2011 Jun;34(6):1431-7.
http://www.ncbi.nlm.nih.gov/pubmed/21617112
Metformin (renal impairment): SAMF, 2014.
viii
Glimepiride: Contract circular HP09-2014SD. http://www.health.gov.za/
Glimepiride: SAMF, 2014.
ix
Insulin therapy (Type 2 diabetes mellitus): Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill
MM, Dave JA, Distiller LA, Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D,
Joshi P, Khutsoane DT, Levitt NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S,
Raubenheimer PJ, Randeree HAR, Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012
SEMDSA Guideline for the Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1S95. http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
x
Aspirin: De Berardis G, Sacco M, Strippoli GF, Pellegrini F, Graziano G, Tognoni G, Nicolucci A. Aspirin for
primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials.
BMJ. 2009 Nov6;339:b4531. http://www.ncbi.nlm.nih.gov/pubmed/19897665
Aspirin: Contract circular HP09-2014SD. http://www.health.gov.za/
xi
ACE-inhibitor: ACEI (ACE Inhibitors in Diabetic Nephropathy Trialist Group) (2001). Should all patients with type
1 diabetes mellitus and microalbuminuria receive angiotensin converting enzyme inhibitors? A meta‐analysis of
individual patient data, Annals of Internal Medicine, 134(5): 370–379.
http://www.ncbi.nlm.nih.gov/pubmed/11242497
xii
Home blood glucose monitoring: Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, Cushman
WC, Genuth S, Ismail-Beigi F, Grimm RH. et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J
Med.2008;358(24):2545–2559. http://www.ncbi.nlm.nih.gov/pubmed/18539917
Home blood glucose monitoring: Östgren CJ, Sundström J, Svennblad B, Lohm L, Nilsson PM, Johansson G.
Associations of HbA1c and educational level with risk of cardiovascular events in 32,871 drug-treated patients with
Type 2 diabetes: a cohort study in primary care. Diabet Med. 2013 May;30(5):e170-7.
http://www.ncbi.nlm.nih.gov/pubmed/23350893
xiii
Dextrose 50%, IV: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA,
Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt
NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR,
Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
xiv
Dextrose 5%: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill MM, Dave JA, Distiller LA,
Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D, Joshi P, Khutsoane DT, Levitt
2015
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ENDOCRINE SYSTEM
NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S, Raubenheimer PJ, Randeree HAR,
Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012 SEMDSA Guideline for the
Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1-S95.
http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
Dextrose 5% in sodium chloride 0.9%, IV: Amod A, Ascott-Evans BH, Berg GI, Blom DJ, Brown SL, Carrihill
MM, Dave JA, Distiller LA, Ganie YN, Grobler N, Heilbrunn AG, Huddle KRL, Janse van Rensburg G, Jivan D,
Joshi P, Khutsoane DT, Levitt NS, May WM, Mollentze WF, Motala AA, Paruk IM, Pirie FJ, Raal FJ, Rauff S,
Raubenheimer PJ, Randeree HAR, Rheeder P, Tudhope L, Van Zyl DJ, Young M; Guideline Committee. The 2012
SEMDSA Guideline for the Management of Type 2 Diabetes (Revised) JEMDSA 2012;17(2)(Supplement 1): S1S95. http://www.semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf
xv
Enoxaparin: Wein L, Wein S, Haas SJ, Shaw J, Krum H. Pharmacological venous thromboembolism prophylaxis
in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Jul
23;167(14):1476-86. http://www.ncbi.nlm.nih.gov/pubmed/17646601
xvi
Pamidronic acid, IV: Body JJ, Pot M, Borkowski A, Sculier JP, Klastersky J. Dose/response study of
aminohydroxypropylidene bisphosphonate in tumor-associated hypercalcemia. Am J Med. 1987 May;82(5):957-63.
http://www.ncbi.nlm.nih.gov/pubmed/3578365
xvii
Hypothyroidism in pregnancy: Vadiveloo T, Mires GJ, Donnan PT, Leese GP. Thyroid testing in pregnant
women with thyroid dysfunction in Tayside, Scotland: the thyroid epidemiology, audit and research study (TEARS).
Clin Endocrinol (Oxf) 2013; 78:466. http://www.ncbi.nlm.nih.gov/pubmed/22548296
Hypothyroidism in pregnancy: Yassa L, Marqusee E, Fawcett R, Alexander EK. Thyroid hormone early
adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab 2010; 95:3234.
http://www.ncbi.nlm.nih.gov/pubmed/20463094
Hypothyroidism in pregnancy: Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR.
Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism.
N Engl J Med. 2004 Jul 15;351(3):241-9. http://www.ncbi.nlm.nih.gov/pubmed/15254282
Hypothyroidism in pregnancy: Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt
and
subclinical
hypothyroidism
complicating
pregnancy.
Thyroid.
2002
Jan;12(1):63-8.
http://www.ncbi.nlm.nih.gov/pubmed/11838732
xviii
Calcium: Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR. Calcium intake and risk of
fracture: systematic review. BMJ. 2015 Sep 29;351:h4580. http://www.ncbi.nlm.nih.gov/pubmed/26420387
Vitamin D: Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR. Calcium intake and risk of
fracture: systematic review. BMJ. 2015 Sep 29;351:h4580. http://www.ncbi.nlm.nih.gov/pubmed/26420387
xix
Doxazosin: van der Zee PA, de Boer A. Pheochromocytoma: a review on preoperative treatment with
phenoxybenzamine or doxazosin. Neth J Med. 2014 May;72(4):190-201.
http://www.ncbi.nlm.nih.gov/pubmed/24829175
xx
Carbimazole: SAMF, 2014.
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CHAPTER 9
SYSTEMIC AND HEALTHCARE-ASSOCIATED
INFECTIONS
ANTIMICROBIAL STEWARDSHIP
Antimicrobial stewardship refers to a systematic approach to optimising the
appropriate use of an antibiotic to improve patient outcome and limit
emergence of resistant pathogens, whilst ensuring patient safety. It is one
arm of the national and international response to the increasing public health
crisis of antibiotic resistance. Antibiotics must only be used for bacterial
infections. The following checklist will help optimize prescribing:
1.
2.
3.
4.
5.
6.
Checklist for optimal antibiotic prescribing
Medicine – which is the narrowest-spectrum antibiotic that I can
use to treat this bacterial infection?
Dose – many antibiotics require weight-based dosing and their
dosing depends on renal and/or hepatic function
Dose frequency – dependent on the half-life of the drug and
whether the action of the antibiotic depends on the time above the
MIC or the area under the concentration/time curve. Guidance for
dosing frequency may require therapeutic drug monitoring, such as
for vancomycin or aminoglycosides.
Duration – should be dictated by evidence from randomised
controlled trials whenever possible. Expert opinion from national
and international guidelines should be consulted where evidence is
weak.
Route – most antibiotics have good oral bioavailability, but some
infections will require intravenous therapy either for the whole or
part of the course.
De-escalation – applies to the spectrum of antibiotic use and route
of administration. All attempts to convert early from parenteral to
oral use should be made.
MIC = minimum inhibitory concentration.
9.1 HEALTHCARE-ASSOCIATED AND HOSPITAL
ACQUIRED INFECTIONS
T80–88
DEFINITION AND PRINCIPLES
Patients with healthcare associated and hospital acquired infections are at
increased risk of being infected with drug resistant organisms. A hospital
acquired infection is a new infection that develops after at least 48 hours of
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hospitalisation, there must be no evidence that the infection was present or
incubating at the time of admission. Healthcare associated infections should
be considered in persons with extensive healthcare contact such as:
residence in a nursing home or other long-term care facility, hospitalization in
an acute care hospital for >2 days during the prior 90 days, or attendance at
a hospital or hemodialysis clinic during the prior 30 days.
It is essential to obtain specimens for culture and sensitivity testing in
all cases before starting antibiotics.
Empiric therapy suggestions below are only rough guidelines due to
heterogenity of resistance patterns between facilities and over time. Close
liaison with regional microbiologists and regular review of hospital antibiotic
policy based on local resistance patterns are essential.
9.1.1 INTRAVASCULAR CATHETER INFECTIONS
T80.2
PERIPHERAL LINE INFECTION:
Common organisms:
» coagulase negative staphylococci particularly S. epidermis
» S. aureus
The intravascular line should always be removed.
Small localised area of erythema at the catheter insertion site will usually
resolve without antibiotic therapy.
In patients with larger areas of erythema and tenderness extending beyond
the insertion site that are systemically well:
i
LoE:III

Clindamycin, oral, 450 mg 8 hourly for 5 days.
If patients with peripheral or central venous catheter infections are
systemically unwell they should be treated as a venous catheter related
systemic blood infection.
Microbiologic specimen: peripheral blood culture, blood culture from central
catheter prior to removal, and culture of the catheter tip.
MEDICINE TREATMENT
Empiric antibiotic therapy
Duration of antibiotic therapy should generally be for 48–72 hours after
resolution of fever except for:
» confirmed S. aureus infection, and
» candidaemia, where treatment should be continued for 2 weeks after the
st
ii
1 negative blood culture.
LoE:III
Note: For candidaemia and S aureues infection, perform blood cultures
every 2-3 days after therapy has been initiated until 2 consecutive cultures
st
are negative, and 2 weeks after the 1 negative blood culture.
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SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
S. aureus infection

Empirically vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20
mg/kg/dose 12 hourly. (See Appendix I for guidance on prescribing and
monitoring).
iii
o Tailor therapy to drug-susceptibility results.
LoE:III
Candidaemia
Note: Candida isolated from blood culture should always be treated, even if
the fever has settled after line removal because of a high risk of late
complications.
st
Treatment duration should be 2 weeks after 1 negative blood culture:
iv
LoE:III

Amphotericin B, IV, 0.7 mg/kg daily.
o Ensure adequate hydration to minimise
nephrotoxicity. (See Appendix I for preventing, monitoring and
v
management of toxicity).
LoE:III
Once improved, complete course with:

Fluconazole, oral, 800 mg daily.
vi
LoE:III
Intolerance to amphotericin B:

Fluconazole, oral, 800 mg daily
Renal failure:

Fluconazole, oral, dose adjusted according to eGFR.
vii
LoE:III
9.1.2 SURGICAL WOUND INFECTIONS
T81
DESCRIPTION
Common organism: S. aureus.
Microbiologic specimen: deep wound swab or aspirate of pus, and blood culture.
Antibiotics are not usually necessary.
MEDICINE TREATMENT
Empiric antibiotic therapy
If surrounding cellulitis or systemic sepsis:
Total duration of therapy: 7 days.
Parenteral therapy:

Cloxacillin, IV, 2 g 6 hourly.
Switch to oral therapy as soon as possible:

Flucloxacillin, oral, 500 mg 6 hourly.
Severe penicillin allergy:

Clindamycin, IV, 600 mg 8 hourly.
Switch to oral therapy as soon as possible:

Clindamycin, oral, 450 mg 8 hourly.
2015
viii
LoE:III
9.3
CHAPTER 9
SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
Methicillin (cloxacillin) reistant S. aureus (MRSA)

Vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20
mg/kg/dose 12 hourly. (See Appendix I for guidance on prescribing and
monitoring).
If surgery was on female uro-genital tract or open GIT surgery:

Ceftriaxone, IV, 2 g daily for 7 days.
AND
ix
LoE:III

Metronidazole, IV, 500 mg 8 hourly for 7 days.
9.1.3 HOSPITAL-ACQUIRED PNEUMONIA (HAP)
J13/J15.9
DESCRIPTION
HAP is defined as a lower respiratory tract infection that was not present on
admission, occurring >48 hours after admission to hospital. HAP has a high
morbidity and mortality and early appropriate antibiotic therapy is essential.
Infection is often due to multi drug resistant organisms particularly in patients
with any of the following risk factors:
» Hospitalised > 5 days,
» Hospitalised for > 2 days in the past 3 months.
» Immunocompromised with poor functional status.
» Developed pneumonia after admission to ICU.
Microbiologic specimen: blood culture and sputum/tracheal aspirate bacterial
culture. Therapy should be adjusted according to culture result.
MEDICINE TREATMENT
Empiric antibiotic therapy
HAP with no risk factors for MDR infection:

Ceftriaxone, IV, 2 g daily.
AND

Amikacin, IV, 15 mg/kg daily.
Severe Penicillin allergy:

Moxifloxacin, oral/IV, 400 mg daily.
AND

Amikacin, IV, 15 mg/kg daily.
HAP with risk factors and ventilator associated pneumonia.
Choice will depend on local susceptibility patterns. One or more of the
following antibiotics/classes must be available:

Piperacillin/tazobactam, IV, 4.5 g 8 hourly.
AND

Amikacin, IV, 15 mg/kg daily.
x
LoE:III
2015
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SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
OR
Instead of piperacillin/tazobactam + amikacin:

Carbapenem with activity against Pseudomonas, e.g.:

Imipenem, IV, 1 g 8 hourly (except CNS infections or known epileptics).
xi
LoE:III
OR
Instead of piperacillin/tazobactam + amikacin OR imipenem:

Meropenem, IV, 2 g 8 hourly (CNS infections or known epileptics).
9.1.4 URINARY
TRACT
ASSOCIATED
INFECTIONS,
CATHETER
N39.0
DESCRIPTION
Common organisms:
» resistant aerobic Gram-negative organisms.
Microbiologic specimen: blood culture and MSU/CSU for microscopy and
bacterial culture.
In most patients with longterm catheters bacteria cultured on CSU represent
colonisation rather than infection – only treat with antibiotics if there are
features of sepsis or pyelonephritis.
GENERAL MEASURES
Remove catheter.
MEDICINE TREATMENT
Empiric antibiotic therapy (Duration of therapy 7–14 days):

Amikacin, IV, 15 mg/kg daily.
OR
If local resistance patterns show low level resistance to ciprofloxacin:
xii
LoE:III

Ciprofloxacin, oral, 500 mg 12 hourly.
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9.2 ADULT VACCINATION
Vaccine

Influenza
vaccine

Pneumococcal
vaccine (23
valent
polysaccharide)
Indications
Comments
» Elderly patients > 65 years.
» HIV-infected patients.
o Contraindication: egg
» Patients with chronic
allergy.
pulmonary, cardiac, and renal
o Dose: IM, 0.5 mL.
conditions.
Repeat annually.
» healthcare workers with direct
patient contact.
o Contraindication:
pregnancy.
o Dose: IM, 0.5 mL.
» Asplenic patients.
Booster: after 5 years
» Chronic cerebrospinal fluid
and at 65 years of
(CSF) leak.
age.
LoE:IIIxiii
o Dose: IM, 1 mL

Hepatitis B
vaccine*
» High risk groups, e.g. hospital
personnel or sexual contacts
of infected patients.
» Sexual assault.
immediately then 1 mL
after 1 month and 1
mL 6 months after 1st
dose .
o Administer deep IM in
deltoid muscle.
Booster when there is a high risk
for tetanus e.g. contaminated
 Tetanus toxoid wound or pregnant women to
o Dose: IM, 40 iu (0.5 mL).
vaccine
prevent neonatal tetanus.
(See trauma section).
* Not to be given to patients who have already been immunised.
9.2.1 RABIES VACCINATION
Z24.2
For prevention of disease in patient exposed to a suspected rabid animal, it
is important to estimate risk of rabies first by assessment of the following:
» type of contact (higher risk for penetrating bites or scratches),
» incidence of rabies in the animal's district of origin,
» higher risk with abnormal animal behaviour,
» species of animal involved.
> High risk: domestic dog, cat, cattle, black backed jackal, bat eared
fox, mongoose species, amongst others.
> Higher risk: if animal not vaccinated.
» when the biting animal cannot be found, or the brain is not available for
laboratory examination, it should be assumed that the animal was infected
Note: If animal is still well with no symptoms ≥ 10 days after exposure, or if
the animal’s brain shows no rabies, post-exposure prophylaxis is not needed
or can be discontinued.
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Patient not previously immunised
Active immunisation with human diploid cell vaccine:

Rabies inactivated whole virus vaccine, IM.
o Administer 1 dose on 0, 3, 7 and14 days post exposure, according to
the standard or essential schedule.
th
o If the patient is immunocompromised: administer 5 dose on day 28.
o Administer vaccine by deep IM injection in the deltoid region and not
the thigh or buttock.
xiv
Caution: Anaphylaxis.
LoE:III
If patient presents after 48 hours, administer double the initial
dose on day 0.
AND
Passive immunisation, for temporary prophylaxis with human rabies
immunoglobulin (HRIG):

HRIG, 20 units/kg on day 0 or within 7 days after giving the first active
vaccine dose.
o Infiltrate around the wound with the largest proportion of the dose.
o Administer the rest of the dose IM.
It is recommended that HRIG be given simultaneously with the first vaccine
dose (day 0) but into a different injection site. HRIG should not be given >7
days after exposure or in patients previously immunised.
Patient previously immunised

Rabies inactivated whole virus vaccine, IM.
o Administer 1 dose on day 0 and day 3.
In these cases HRIG (see above) is not given.
Caution: Anaphylaxis.
If patient presents after 48 hours, double initial dose on day zero.
Risk
Category
1
Type of exposure
»
»
2
»
»
3
2015
Action
Touching or feeding
animal.
Licking intact skin.
None if reliable history.
Nibbling uncovered
skin.
Superficial scratch
without bleeding.
Wound treatment.
Give rabies vaccine.
Do not give HRIG, except in HIV
infected people.
Stop vaccination if laboratory tests
of animal are negative for rabies or
animal remains well after 10 days
observation.
»
Licking broken skin.
»
Bites or scratches
penetrating skin and
drawing blood.
Wound treatment.
Give rabies vaccine.
Give HRIG.
9.7
CHAPTER 9
SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
»
Licking of mucous
membranes.
Give tetanus toxoid vaccine and
antibiotic.
Stop vaccination if laboratory tests
of animal are negative for rabies or
animal remains well after 10 days
observation.
Rabies Vaccine
Must be given for category 2 and 3 bites.
Administer the vaccine on days 0, 3, 7 and 14.
th
If the patient is immunocompromised: administer 5 dose on day 28.
Ideally, the vaccine should be given as soon as possible after exposure, but
should still be given if patient presents some time after the exposure.
If vaccine administration is delayed > 48 hours, give an initial double dose.
Administer rabies vaccine IM, never in the buttock. In adults, give the
vaccine into the deltoid muscle.
HRIG
Must be given for category 3 bites only.
However, in the HIV-infected administer HRIG for category 2 bites.
Always give the vaccine first.
Immunoglobulin must be given as soon as possible after exposure, but may
be administered up to 7 days after the first vaccine is given.
Do not give HRIG if the patient has previously received pre- or post-exposure
prophylaxis.

HRIG, 20 units/kg.
o Infiltrate around wound with the largest proportion of the dose.
o Administer remaining immunoglobulin into deltoid muscle opposite
to vaccine administration site.
o If multiple wounds, dilute in sodium chloride 0.9% to 2–3 times so
that all wounds are infiltrated.
o Do not exceed maximum dose as antibody production to the
vaccine is inhibited.
o If unavailable, do not delay active immunisation.
9.3 BRUCELLOSIS
A23.1
*This is a notifiable disease.
DESCRIPTION
Zoonotic infection, usually due to B. abortus in South Africa. Infection is
usually acquired from unpasteurised milk products or handling raw meat.
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MEDICINE TREATMENT
Exclude TB before starting therapy.

Doxycycline, oral, 100 mg 12 hourly for 6 weeks.
AND

Gentamicin, IV, 6 mg/kg daily for 3 weeks.
(Preferred regimen for osteo-articular or cardiac involvement.)
xv
LoE:III
OR

Doxycycline, oral, 100 mg 12 hourly for 6 weeks.
AND

Rifampicin, oral, 7.5 mg/kg 12 hourly for 6 weeks.
9.4 HAEMORRHAGIC FEVER SYNDROME
A98.0
Severe bacterial infections can mimic the features of haemorrhagic fever
syndrome, and broad spectrum antibiotics, e.g. ceftriaxone, IV, 2 g daily,
are indicated in every case until the diagnosis is confirmed.
DESCRIPTION
High fever, together with disseminated intravascular coagulation (DIC) and
bleeding tendency. Other symptoms and organ involvement vary according
to the causative virus.
Some important causes other than viral haemorrhagic fevers (VHF) are:
» severe bacterial infections, particularly N. meningitidis,
» severe tick bite fever,
» severe falciparum malaria,
» fulminant hepatitis,
» leptospirosis, and
» other causes for DIC or bleeding tendency.
Endemic causes of VHF in South Africa are Crimean-Congo fever and Rift
Valley Fever, both of which may be transmitted between humans by means of
blood and body fluids.
REFERRAL
All suspected VHF cases need to be discussed and managed in consultation
with the Regional Virologist or Infectious Diseases Consultant at the referral
centre.
Cases may also be discussed with the Special Pathogens Unit of the
National Institute for Communicable Diseases (NICD):
Tel: 011 386 6000, Outbreak hotline: 082 883 9920
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Transfer of patients will only occur once all relevant arrangements have
been made to limit further exposure to a potentially contagious and life
threatening virus.
MANAGEMENT
A detailed travel and clinical history is crucial. If VHF is still considered,
isolate patient in a single room and take proper precautions to limit further
exposure. These include:
» long sleeved disposable gown,
» vinyl or rubber apron if the patient is bleeding,
» two pairs of latex gloves, one below the gown and one over the gown,
» disposable face mask preferably with a visor,
» goggles if a mask without the visor is used, and
» waterproof boots or 2 pairs of overshoes, one over the other.
Exclude alternate diseases (see above) by means of appropriate laboratory
testing.
Support patients with packed red cells and fresh frozen plasma, as required.
Testing for VHF may be required, both to confirm or exclude the possibility of
VHF - this must be arranged with the NICD (see above), before sending the
specimens, as specific precautions apply.
Record and follow up all patient contacts.
9.5 HYDATID DISEASE
B67
DESCRIPTION
Cysts of E. granulosus, acquired from ingestion of helminth ova passed out
in dog faeces, particularly in sheep-farming areas. Cysts may occur in any
organ, but are most commonly found in the liver and lungs.
MEDICINE TREATMENT

Albendazole, oral, 15 mg/kg/day up to maximum of 400 mg 12 hourly
with a fatty meal (e.g. a glass of full cream milk), for 3–6 months
xvi
according to response on imaging.
LoE:III
o Monitor liver function tests and full blood counts
monthly.
With medical therapy as above, cure is achieved in about half, improvement
in about a quarter and no response in about a quarter of cases.
Definitive treatment with surgery or PAIR (percutaneous aspiration injection
of helminthicidal agent and re-aspiration) is preferred for all accessible
lesions.
Before PAIR or surgery:

Albendazole, oral, 15 mg/kg/day or 200 mg 12 hourly, up to maximum of
400 mg per day with a fatty meal (e.g. a glass of full cream milk), for 14
to 28 days.
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o
SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
Follow with 28 days after surgery.
xvii
LoE:I
REFERRAL
All cases to a centre with experience in surgery and PAIR.
9.6 MALARIA
9.6.1 MALARIA, NON-SEVERE
B54
*This is a notifiable disease.
DESCRIPTION
The most important element in the diagnosis of malaria is a high index of
suspicion. Test any person resident in, or returning from, a malaria area and
who presents with fever (usually within 3 months of exposure). Malaria may
also occur in people bitten by mosquitoes travelling from endemic areas in
aeroplanes or vehicles, or from blood transfusion. The progression to severe
falciparum malaria may be rapid, therefore early diagnosis and effective
treatment is crucial.
Pregnant women and young children up to 5 years of age are at high
risk of developing severe malaria.
Clinical features include:
» severe headache,
» fever above 38C,
» muscle and joint pains,
»
»
»
shivering attacks,
nausea and vomiting,
flu-like symptoms.
Progression to severe malaria may occur – see section 9.6.2: Malaria,
severe.
Diagnosis
» Microscopic examination of thick and thin blood smears. Thick films are
more sensitive than thin films in the detection of malaria parasites.
» One negative malaria test does not exclude the diagnosis of malaria.
nd
Request a 2 test.
» Where rapid diagnostic tests are available, e.g. plasma reagent
dipsticks, these can be used to diagnose malaria within 10–15 minutes.
Rapid tests may remain positive for up to 1 month after successful
treatment.
Note: If neither microscopy nor rapid tests are available diagnosis should be
made on the basis of clinical symptoms.
GENERAL MEASURES
Provide supportive and symptomatic relief.
Monitor for complications.
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Beware of over-hydration.
All patients with P. falciparum malaria should be carefully observed for the first
24 hours.
MEDICINE TREATMENT
Vomiting oral treatment is one of the commonest reasons for treatment
failure. If vomiting is a presenting symptom, the patient has severe malaria
and needs IV therapy (see 9.6.2). Give all first doses of oral medicines
under supervision and observe patients for at least an hour. Repeat the
oral treatment or give IV treatment if the patient vomits within the first
hour.
Malaria should be treated at primary health care level in areas of South
Africa where malaria occurs seasonally. In other areas, patients should be
referred to a hosptal for treatment.
Uncomplicated P. falciparum malaria in South Africa
(If unsure of species, treat as for P. falciparum malaria)

Artemether/lumefantrine 20/120 mg, oral, 4 tablets/dose with fat
containing food or full cream milk to ensure adequate absorption
o Give the first dose immediately.
o Follow with second dose 8 hours later.
o Then 12 hourly for another 2 days. (Total number of doses in 3
days = 6; i.e. 24 tablets).
REFERRAL
»
»
Patients not responding to oral treatment within 48 hours.
Patients with P. vivax and P. ovale malaria.
9.6.2 MALARIA, SEVERE
B50.0
*This is a notifiable disease.
See section 9.6.1: Malaria, Non-severe for uncomplicated malaria and
primary care book for non-falciparum malaria.
DESCRIPTION
P. falciparum malaria with one or more of the following features:
» impaired consciousness
» renal dysfunction
» convulsions
» heavy parasitaemia ( 5%)
» vomiting
» ARDS
» severe anaemia (Hb < 6 g/dL)
» shock
» haemoglobinuria
» hypoglycaemia
» acidosis (plasma bicarb <15 » clinical jaundice
mmol/L)
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GENERAL MEASURES
Maintain hydration but avoid excessive fluid administration as this could
contribute to the development of ARDS (especially in pregnancy).
Transfuse if haemoglobin < 6 g/dL.
There is no convincing evidence of benefit for the use of exchange
transfusion.
MEDICINE TREATMENT
Intravenous therapy:
The preferred agent is parenteral artesunate:

Artesunate IV, 2.4 mg/kg at 0, 12 and 24 hours; then daily until patient is
able to tolerate oral therapy.
o Administer at least 3 IV doses before switching to oral
artemether/lumefantrine.
xviii
LoE:I
If parenteral artesunate is not available:

Quinine, IV (1 mL = 300 mg quinine salt).
o Loading dose: 20 mg/kg in dextrose 5% administered over 4 hours.
o Maintenance dose: 8 hours after start of the loading dose, give 10
mg/kg in dextrose 5% over 4 hours repeated every 8 hours until
there is clinical improvement and the patient can take oral therapy.
o Monitor for hypoglycaemia and dysrhythmias at least 4 hourly.
o If there is significant renal failure increase dose interval to 12 hourly
after 48 hours.
Follow intravenous therapy with oral therapy:

Artemether/lumefantrine 20/120 mg, oral, 4 tablets/dose with fatcontaining food or full cream milk to ensure adequate absorption.
o Give the first dose immediately.
o Give the second dose 8 hours later.
o Then 12 hourly for another 2 days. (Total number of doses in 3
days = 6; i.e. 24 tablets).
Monitor treatment response with regular blood smears.
An increase in parasitaemia may occur within 24 hours due to release of
sequestrated parasites, but a reduction should be seen after 48 hours.
Note: Gametocytes may appear after this stage – this does NOT mean
failure of therapy as gametocytes may persist for up to 2 weeks after
successful therapy.
Only the reappearance of, or failure to clear, trophozoites means failure.
Consider concomitant bacteraemia in patients with severe malaria,
especially if they have neutrophilia.
REFERRAL
Patient in need of ventilation or dialysis if these are unavailable on site.
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9.7 TETANUS
A35
*This is a notifiable disease.
GENERAL MEASURES
Maintain airway.
Monitor ECG and blood pressure.
Maintain and replace IV fluids.
Wound management is essential with debridement and removal of any
foreign bodies.
Alleviate fever with mechanical cooling methods.
MEDICINE TREATMENT
For rigidity, spasms:

Diazepam, IV, 10 mg 4 hourly, for 24 hours, then consider oral route as
high doses of parentral diazepam can cause an acidosis.
xix
LoE:I
o Titrate to effect.
o Doses as high as 50–100 mg 2 hourly are
sometimes required.
Muscle relaxants should be used sparingly and may exacerbate autonomic
instability.
Antibiotic treatment:

Benzylpenicillin (penicillin G), IV, 5 MU 6 hourly for 10 days.
OR

Metronidazole, IV, 500 mg 8 hourly for 10 days.
For passive immunisation:

Tetanus immunoglobulin, IM, 3 000 units as a single dose.
For active immunisation of all patients: (as clinical tetanus does not always
confer immunity)

Tetanus toxoid vaccine, IM, 0.5 mL, total of 3 doses:
o on admission,
o at 4 weeks, and
o at 6 months.
o Administer at a different site to that used for administering tetanus
immunoglobulin.
For fever:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
For shock, dehydration, maintenance of hydration:

IV fluids.
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SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
For prophylaxis for deep vein thrombosis:

Unfractionated heparin, SC, 5 000 units 12 hourly.
OR

Enoxaparin, SC, 40 mg daily.
xx
LoE:I
For pain:

Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
REFERRAL
All cases to a facility with resources for artificial ventilation.
9.8 TICK BITE FEVER
A79.9
DESCRIPTION
Tick-borne infection due to R. conorii, acquired from dogs, or R. africae,
acquired from cattle and game. The hallmark of tick bite fever is the eschar,
i.e. a round black lesion ± 5 mm in diameter with an inflammatory halo,
occurs in about two thirds of patients with R. conorii and in most cases of R.
africae infection, where multiple eschars are common. A rash develops on
about the third day of illness in about two thirds of patients with R. conorii
and in fewer cases of R. africae infection. In R. conorii infection the rash is
maculopapular and involves the palms and soles. In R. africae infection the
rash is sparse and may be vesicular.
MEDICINE TREATMENT

Doxycycline, oral, 100 mg 12 hourly for 7 days.
In pregnancy:

Azithromycin, oral, 500 mg 12 hourly for 3 days.
o In severe cases, initiate therapy with 1–2 days of doxycycline.
xxi
LoE:III
For the rare patient unable to take oral therapy:
Total duration of therapy: 7 days.
xxii
LoE:III

Ciprofloxacin, IV, 400 mg 8 hourly.
Note: This is inferior to doxycycline, which should be
commenced as soon as possible.
9.9 ENTERIC FEVER (TYPHOID)
A01.0
*(Typhoid fever) This is a notifiable disease.
DESCRIPTION
Systemic infection due to S. enteritica serotype Typhi or related organisms
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(e.g. S. paratyphi, S. choleraesuis). Initial symptoms are abdominal pain,
headache, cough and fever, with diarrhoea developing after a few days.
Bacteraemia is common in the first week of illness, subsequently stool
culture has the highest yield.
GENERAL MEASURES
Transfusion is indicated for severe haemorrhage.
Replace fluid and electrolytes.
MEDICINE TREATMENT
Antibiotic therapy
There is increasing resistance to ciprofloxacin in South Africa and it
is important to send specimens for culture and sensitivity prior to
commencing antibiotic therapy.
Total duration of antibiotic therapy: 10 days.

Ceftriaxone, IV, 2 g 12 hourly.
xxiii
LoE:II
Switch to oral therapy as soon as possible and based on culture sensitivity
results:
LoE:III

Ciprofloxacin, oral, 500 mg 12 hourly.
Stool cultures must be repeated at weekly intervals after convalescence to
ensure that a carrier state has not developed. Two consecutive negative
stool cultures are required to exclude carrier state. This is of vital importance
in food handlers, who must not be permitted to return to work until stools are
negative.
Chronic carriers:

Ciprofloxacin, oral, 500 mg 12 hourly for 6 weeks (if sensitive to
ciprofloxacin).
REFERRAL
Surgical consultation for complications such as intestinal haemorrhage,
threatening bowel perforation or localisation with metastatic infection with or
without abscess formation, and peritonitis.
9.10 VARICELLA (CHICKENPOX), COMPLICATED
B01
GENERAL MEASURES
Cool, wet compresses or tepid water baths.
Body hygiene to prevent secondary infection.
Advise against scratching.
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MEDICINE TREATMENT
Antiviral therapy is required in complicated cases, e.g.:
» chickenpox pneumonia,
» pregnancy,
» neurological involvement, and
» chickenpox in immunocompromised patients.

Aciclovir, IV, 10 mg/kg administrerd over one hour 8 hourly for 7 days.
o The course can be completed with aciclovir, oral, 800 mg five times
daily.
For patients who are severely immunologically compromised and are not
immune:

Varicella-zoster immunoglobulin (VZIG), IM, 125 units/10 kg.
o Maximum dose: 625 units.
o Administer within 96 hours after significant exposure.
9.11 ZOSTER (SHINGLES)
B01.8
DESCRIPTION
Dermatomal eruption of vesicles on an erythematous base due to varicellazoster virus (lies dormant in nerve ganglia following chickenpox).
GENERAL MEASURES
Isolate from immunocompromised or pregnant non-immune individuals (who
may develop severe chickenpox).
Offer HIV test, especially in patients < 50 years of age.
MEDICINE TREATMENT
Antiviral therapy, for:
» zoster in immunocompromised patients, provided that active lesions are
still being formed, and
» in immunocompetent individuals provided they present within 72 hours
of onset.

Aciclovir, oral, 800 mg five times daily for 7 days (4 hourly missing the
middle of the night dose).
For zoster with secondary dissemination or neurological involvement:

Aciclovir, IV, 10 mg/kg administred over one hour 8 hourly for 7 days.
o The course can be completed with aciclovir, oral, 800 mg five times
daily.
Eye involvement:
ADD

Aciclovir opthalmic ointment 3%, applied into lower conjunctival sac, five
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SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
times daily.
Secondary infection
This is seldom present and is over-diagnosed. The vesicles in shingles often
contain purulent material, and erythema is a cardinal feature of shingles. If
there is suspected associated bacterial cellulitis:

Flucloxacillin, oral, 500 mg 6 hourly for 5 days.
For pain:
Pain is often very severe and requires active control. Combination of
different classes of analgesics is often necessary.
Recommended therapy for acute phase of infection, e.g.:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
AND/OR
If pain is not adequately controlled:

Tramadol, oral, 50 mg 6 hourly.
o If response not adequate, increase dose to 100 mg 6 hourly.
See section 12.13: Pain, chronic.
Post-herpetic neuralgia:
Initiate treatment with adjuvant therapy early.

Amitriptyline, oral, 25 mg at night.
o Titrate as necessary to a maximum of 75 mg.
See section 12.13: Pain, Chronic.
REFERRAL
Refer to an ophthalmologist if there is ocular involvement with ophthalmic
zoster (if the tip of the nose is involved then ocular involvement is much
more likely). See section 18.4: Herpes zoster ophthalmicus.
References:
i
Clindamycin, oral: South African Antibiotic Stewardship Programme. A Pocket Guide to Antibiotic Prescribing for
Adults in South Africa, 2015. http://www.fidssa.co.za/images/SAASP_Antibiotic_Gudidelines_2015.pdf
Clindamycin, oral: SAMF, 2014
Clindamycin, oral: Bouazza N, Pestre V, Jullien V, Curis E, Urien S, Salmon D, Tréluyer JM. Population
pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis. Br J Clin
Pharmacol. 2012 Dec;74(6):971-7. http://www.ncbi.nlm.nih.gov/pubmed/22486719
ii
Empiric parenteral antibiotic therapy (S. aureus infection): Chong YP, Moon SM, Bang KM, Park HJ, Park SY,
Kim MN, Park KH, Kim SH, Lee SO, Choi SH, Jeong JY, Woo JH, Kim YS. Treatment duration for uncomplicated
Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study.
Antimicrob Agents Chemother. 2013 Mar;57(3):1150-6. http://www.ncbi.nlm.nih.gov/pubmed/23254436
Empiric parenteral antibiotic therapy (S. aureus infection): Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK,
Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious
Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the
treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb
1;52(3):e18-55. http://www.ncbi.nlm.nih.gov/pubmed/21208910
2015
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iii
Vancomycin, IV: Reardon J, Lau TT, Ensom MH. Vancomycin loading doses: a systematic review. Ann
Pharmacother. 2015 May;49(5):557-65. http://www.ncbi.nlm.nih.gov/pubmed/25712445
Vancomtcin, IV: Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR,
Levine DP. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of
Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases
Pharmacists. Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. Erratum in: Am J Health Syst Pharm. 2009 May
15;66(10):887. http://www.ncbi.nlm.nih.gov/pubmed/19106348
iv
Antibiotic therapy (candidaemia): Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, Kohno S;
ACTIONs Project. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J
Antimicrob Chemother. 2015 Feb;70(2):587-93. http://www.ncbi.nlm.nih.gov/pubmed/25326087
v
Amphotericin B, IV: Rex JH, Bennett JE, Sugar AM, Pappas PG, van der Horst CM, Edwards JE, Washburn
RG, Scheld WM, Karchmer AW, Dine AP, et al. A randomized trial comparing fluconazole with amphotericin B for
the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N
Engl J Med. 1994 Nov 17;331(20):1325-30. http://www.ncbi.nlm.nih.gov/pubmed/7935701
Amphotericin B, IV: Phillips P, Shafran S, Garber G, Rotstein C, Smaill F, Fong I, Salit I, Miller M, Williams K,
Conly JM, Singer J, Ioannou S. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of
candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis. 1997
May;16(5):337-45. http://www.ncbi.nlm.nih.gov/pubmed/9228472
Amphotericin B, IV: Anaissie EJ, Darouiche RO, Abi-Said D, Uzun O, Mera J, Gentry LO, Williams T,
Kontoyiannis DP, Karl CL, Bodey GP. Management of invasive candidal infections: results of a prospective,
randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis.
1996 Nov;23(5):964-72. http://www.ncbi.nlm.nih.gov/pubmed/8922787
Amphotericin B, IV: Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, Kohno S; ACTIONs
Project. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob
Chemother. 2015 Feb;70(2):587-93. http://www.ncbi.nlm.nih.gov/pubmed/25326087
Amphotericin B, IV: WHO. Diagnosis, Prevention and Management of Cryptococcal disease in HIV- infected
Adults, Adolescents and children – 2011. Geneva: World Health Organization; 2011. http://www.who.int/en/
Amphotericin B, IV: Atsmon J, Dolev E. Drug-induced hypomagnesaemia : scope and management. Drug Saf.
2005;28(9):763-88. http://www.ncbi.nlm.nih.gov/pubmed/16119971
Amphotericin B, IV: WHO. Rapid advice: diagnosis, prevention and management of cryptococcal disease in
HIV-infected adults, adolescents and children. 2011 [Online][Accessed June 2015]
http://www.ncbi.nlm.nih.gov/books/NBK299520/pdf/Bookshelf_NBK299520.pdf
vi
Fluconazole, oral: Rex JH, Pappas PG, Karchmer AW. A randomized and blinded multicenter trial of high-dose
fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences
in nonneutropenic subjects. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin
Infect Dis 2001; 36: 1221–8. http://www.ncbi.nlm.nih.gov/pubmed/12746765
Fluconazole, oral: Edwards JE Jr, Bodey GP, Bowden RA, Büchner T, de Pauw BE, Filler SG, Ghannoum MA,
Glauser M, Herbrecht R, Kauffman CA, Kohno S, Martino P, Meunier F, Mori T, Pfaller MA, Rex JH, Rogers TR,
Rubin RH, Solomkin J, Viscoli C, Walsh TJ, White M. International Conference for the Development of a
Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis. 1997 Jul;25(1):4359. Review. http://www.ncbi.nlm.nih.gov/pubmed/9243032
Fluconazole, oral: Andes D, van Ogtrop H. Characterization and quantitation of the pharmacodynamics of
fluconazole in a neutropenic murine disseminated candidiasis infection model. Antimicrob Agents Chemother 1999;
43:2116–20. http://www.ncbi.nlm.nih.gov/pubmed/10471550
vii
Fluconazole, oral (renal failure): SAMF, 2014.
viii
Empiric antibiotic therapy (surgical wound infections): Stevens DL, Bisno AL, Chambers HF, Dellinger EP,
Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines for the
diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of
America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. Erratum in: Clin Infect Dis. 2015 May 1;60(9):1448. Dosage
error in article text. http://www.ncbi.nlm.nih.gov/pubmed/24973422
ix
Empiric antibiotic therapy (surgical wound infections): Stevens DL, Bisno AL, Chambers HF, Dellinger EP,
Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines for the
diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of
America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. Erratum in: Clin Infect Dis. 2015 May 1;60(9):1448. Dosage
error in article text. http://www.ncbi.nlm.nih.gov/pubmed/24973422
Ceftriaxone, IV (Surgery on female uro-genital tract/ open GIT surgery): Stevens DL, Bisno AL, Chambers HF,
Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines
for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases
Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. Erratum in: Clin Infect Dis. 2015 May 1;60(9):1448.
Dosage error in article text. http://www.ncbi.nlm.nih.gov/pubmed/24973422
Metronidazole, IV (Surgery on female uro-genital tract/ open GIT surgery): Stevens DL, Bisno AL, Chambers
HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice
guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious
Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. Erratum in: Clin Infect Dis. 2015 May
1;60(9):1448. Dosage error in article text. http://www.ncbi.nlm.nih.gov/pubmed/24973422
x
Piperacillin/taxobactam and amikacin: Nau R, Kinzig-Schippers M, Sörgel F, Schinschke S, Rössing R, Müller
C, Kolenda H, Prange HW. Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of
hydrocephalic patients. Antimicrob Agents Chemother. 1997 May;41(5):987-91.
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CHAPTER 9
SYSTEMIC AND HEALTHCARE-ASSOCIATED INFECTIONS
http://www.ncbi.nlm.nih.gov/pubmed/9145857
xi
Imipenem: SAMF, 2014.
xii
Ciprofloxacin, oral: NHLS/NICD Communicable Diseases Surveillance Bulletin, April 2015 (Volume 13. No 1).
http://www.nicd.ac.za/
xiii
Pneumococcal vaccine (23 valent polysaccharide): ACIP Practice Guidelines - CDC. Morbidity and Mortality
Weekly Report, October 12, 2012, Vol 61, No 40.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6140a4.htm?s_cid=mm6140a4_w
xiv
Rabies vaccine (immunocompetent persons): Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD,
Lett SM, Levis R, Meltzer MI, Schaffner W, Cieslak PR; Centers for Disease Control and Prevention (CDC). Use of
a reduced (4-dose) vaccine schedule for post exposure prophylaxis to prevent human rabies: recommendations of
the advisory committee on immunization practices. MMWR Recomm Rep. 2010 Mar 19;59(RR-2):1-9. Erratum
in:MMWRRecomm Rep. 2010 Apr 30;59(16):493. http://www.ncbi.nlm.nih.gov/pubmed/20300058
Rabies vaccine (immunocompetent persons): Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD,
Lett S, Levis R, Meltzer MI, Schaffner W, Cieslak PR. Evidence for a 4-dose vaccine schedule for human rabies
post-exposure prophylaxis in previously non-vaccinated individuals. Vaccine. 2009 Nov 27;27(51):7141-8.
http://www.ncbi.nlm.nih.gov/pubmed/19925944
Rabies vaccine (immunocompromised persons): World Health Organization.WHO Expert Consultation on
Rabies.2nd report. WHO Technical Report Series, No. 982. Geneva, Switzerland: World Health Organization;
2013. http://apps.who.int/iris/bitstream/10665/85346/1/9789240690943_eng.pdf
xv
Gentamicin: SAMF, 2014.
xvi
Albendazole: Rigter IM, Schipper HG, Koopmans RP, van Kan HJ, Frijlink HW, Kager PA, Guchelaar HJ.
Relative bioavailability of three newly developed albendazole formulations: a randomized crossover study with
healthy volunteers. Antimicrob Agents Chemother. 2004 Mar;48(3):1051-4.
http://www.ncbi.nlm.nih.gov/pubmed/14982808
xvii
Albendazole plus PAIR surgery: Smego RA Jr, Bhatti S, Khaliq AA, Beg MA. Percutaneous aspiration-injectionreaspiration drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: a meta-analysis. Clin
Infect Dis. 2003 Oct 15;37(8):1073-83. http://www.ncbi.nlm.nih.gov/pubmed/14523772
xviii
Artesunate, IV: Artesunate, parenteral: Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for
treating severe malaria. Cochrane Database Syst Rev. 2012 Jun 13;6:CD005967.
http://www.ncbi.nlm.nih.gov/pubmed/22696354
xix
Diazepam: Vassa NT, Doshi HV, Yajnik VH, Shah SS, Joshi KR, Patel SH. Comparative clinical trial of
diazepam with other conventional drugs in tetanus. Postgrad Med J. 1974 Dec;50(590):755-8.
http://www.ncbi.nlm.nih.gov/pubmed/4619836
Diazepam: Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic
illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study.
Chest. 2005 Sep;128(3):1674-81. http://www.ncbi.nlm.nih.gov/pubmed/16162774
xx
Enoxaparin: Wein L, Wein S, Haas SJ, Shaw J, Krum H. Pharmacological venous thromboembolism
prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007
Jul 23;167(14):1476-86. http://www.ncbi.nlm.nih.gov/pubmed/17646601
xxi
Azithromycin, oral (pregnancy): Cascio A, Colomba C, Antinori S, Paterson DL, Titone L. Clarithromycin versus
azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial. Clin Infect
Dis. 2002 Jan 15;34(2):154-8. http://www.ncbi.nlm.nih.gov/pubmed/11740701
xxii
Ciprofloxacin, IV: Raoult D, Drancourt M. Antimicrobial therapy of rickettsial diseases. Antimicrob Agents
Chemother. 1991 Dec;35(12):2457-62. http://www.ncbi.nlm.nih.gov/pubmed/1810178
xxiii
Ceftriaxone, IV: Acharya G, Butler T, Ho M, Sharma PR, Tiwari M, Adhikari RK, Khagda JB, Pokhrel B, Pathak
UN. Treatment of typhoid fever: randomized trial of a three-day course of ceftriaxone versus a fourteen-day course
of chloramphenicol. Am J Trop Med Hyg. 1995 Feb;52(2):162-5. http://www.ncbi.nlm.nih.gov/pubmed/7872445
Ceftriaxone, IV: Smith MD, Duong NM, Hoa NT, Wain J, Ha HD, Diep TS, Day NP, Hien TT, White NJ.
Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever. Antimicrob Agents Chemother.
1994 Aug;38(8):1716-20. http://www.ncbi.nlm.nih.gov/pubmed/7986000
Ceftriaxone, IV: Wallace MR, Yousif AA, Mahroos GA, Mapes T, Threlfall EJ, Rowe B, Hyams KC. Ciprofloxacin
versus ceftriaxone in the treatment of multiresistant typhoid fever. Eur J Clin Microbiol Infect Dis. 1993
Dec;12(12):907-10. http://www.ncbi.nlm.nih.gov/pubmed/8187784
Ceftriaxone, IV: Islam A, Butler T, Kabir I, Alam NH. Treatment of typhoid fever with ceftriaxone for 5 days or
chloramphenicol for 14 days: a randomized clinical trial. Antimicrob Agents Chemother. 1993 Aug;37(8):1572-5.
http://www.ncbi.nlm.nih.gov/pubmed/8215265
Ceftriaxone, IV: Lasserre R, Sangalang RP, Santiago L. Three-day treatment of typhoid fever with two different
doses of ceftriaxone, compared to 14-day therapy with chloramphenicol: a randomized trial. J Antimicrob
Chemother. 1991 Nov;28(5):765-72. http://www.ncbi.nlm.nih.gov/pubmed/1778879
Ceftriaxone, IV: Islam A, Butler T, Nath SK, Alam NH, Stoeckel K, Houser HB, Smith AL. Randomized treatment
of patients with typhoid fever by using ceftriaxone or chloramphenicol. J Infect Dis. 1988 Oct;158(4):742-7.
http://www.ncbi.nlm.nih.gov/pubmed/3171225
2015
9.20
CHAPTER 10
HIV AND AIDS
Consult the most recent HIV Guidelines from the
National Department of Health.
10.1 ANTIRETROVIRAL THERAPY
B20
Combination antiretroviral therapy (ART) consists of ≥ 3 antiretroviral
medicines that are capable of suppressing HIV replication. The current
recommended ART regimen contains 2 nucleoside reverse transcriptase
inhibitors (NRTIs) together with either a non-nucleoside reverse transcriptase
inhibitor (NNRTIs) or a protease inhibitor.
High levels of adherence are essential for long-term success with ART.
ELIGIBILITY FOR ART
Eligibility to start ART:
3
All patients with CD4 count < 500 cells/mm
OR
i
LoE: III
All patients with WHO stage 3 or 4
OR
HIV/hepatitis B co-infection
ii
LoE: III
Immediate initiation:
All pregnant and breastfeeding women, irrespective of CD4 count.
iii
LoE:III
Fast tracking (within 7 days):
3
Patients with CD4 < 200 cells/ mm .
OR
Patients with WHO stage 4, even if CD4 is not yet available.
iv
LoE:III
Timing of ART initiation:
» ART should be started as soon as the patient is ready, and generally
within 2 weeks of CD4 count result availability. However, with some
opportunistic diseases early ART initiation can cause harm by
increasing the risk of the immune reconstitution inflammatory syndrome
(see section 10.1.2: Management of selected antiretroviral adverse drug
reactions).
» In TB co-infection, start with TB treatment first, followed by ART initiation
according to CD4 count (except TB meningitis – see below):
3
- CD4 < 50 cells/mm : Initiate ART within 2 weeks of starting TB treatment.
2015
10.1
CHAPTER 10
HIV AND AIDS
3
»
»
- CD4 > 50 cells/mm : ART initiation may be delayed up to 8 weeks after
starting TB treatment.
v
LoE:I
In patients with TB meningitis (irrespective of CD4
count), defer ART until 8 weeks after initiating TB treatment.
vi
LoE:I
In patients with cryptococcal meningitis, defer ART until
4–6 weeks after starting antifungal treatment (earlier initiation has been
vii
shown to increase the risk of death).
LoE:I
PSYCHOSOCIAL INDICATORS OF READINESS FOR ART
It is essential that patients have good insight into the need for long-term
therapy and high levels of adherence. Give careful attention to adherence
planning. Encourage patients to disclose their HIV status to somebody who
should act as a treatment supporter. If this is not possible then the patient
should join a support group.
Manage depression.
Active substance abuse/alcohol is an impediment to adherence and, if
possible, should be addressed prior to initiating ART.
ART REGIMENS
1
ST
LINE ART
Treatment-naïve patients
Tenofovir (TDF) + Emtricitabine (FTC) +
Efavirenz (EFV)
Contraindications to EFV
» psychiatric co-morbidity
» intolerance to EFV (neuro-psychiatric
toxicity, shift workers)
TDF + FTC + Nevirapine (NVP)*
*Avoid NVP in women with a CD4 count
> 250 cells/mm3 and men with a CD4
count > 400 cells/mm3 at ART initiation
due to increased risk of rash-associated
hepatitis.
Start protease inhibitor based regimen:
TDF + FTC + Lopinavir/ritonavir (LPV/r)
Abacavir (ABC) + lamivudine (3TC) +
EFV or (NVP)
Contraindications to EFV + NVP
Contraindication to TDF
» eGFR <50 mL/min.
» Use of additional nephrotoxic drug e.g.
aminoglycoside.
viii
LoE:I
Contraindication to TDF and ABC
Zidovudine (AZT) + 3TC + EFV or (NVP)
intolerance
» eGFR < 50 mL/min.
» Use of additional nephrotoxic drug e.g.
aminoglycoside.
» Hypersensitivity.
Note: In the unlikely scenario where there is intolerance/contraindication to all currently
available NRTIs (TDF, AZT and ABC), an alternative dual-therapy regimen comprising a
combination of an NNRTI (EFV) and PI (LPV/r) may be used.
Consult a specialist.
2015
10.2
CHAPTER 10
HIV AND AIDS
2
ND
LINE ART
Management of virological failure
If plasma HIV RNA (VL) >1000 copies/mL:
» Assess adherence, tolerability, medicine
interactions & psychosocial factors.
» Repeat VL test 2 months later.
Note: Always check hepatitis B surface
antigen (HBsAg) before stopping TDF:
» If patient has chronic hepatitis B,
stopping TDF may lead to a fatal
hepatitis flare.
» If hepatitis B positive, TDF should be
continued in the 2nd line regimen.
If plasma VL confirmed >1000 copies/mL,
and adherence issues addressed:
» Change regimen to 2nd line therapy.
Failing a TDF-based 1st line regimen
» Patients with anaemia and renal
impairment, switch to ABC.
» Check HBsAg and if positive, continue
TDF with the new regimen.
AZT + 3TC + Lopinavir/Ritonavir (LPV/r)
(PLUS TDF, if HBsAg positive).
Failing a d4T/AZT-based 1st line regimen
TDF + FTC and LPV/r
Dyslipidaemia or diarrhoea associated
with LPV/r
Switch LPV/r to atazanavir (ATV/r)
3
nd
Failing any 2
line regimen
RD
LINE ART
Refer to a specialist.
Resistance to protease inhibitors must be
shown
on
genotype
antiretroviral
resistance test in order to qualify for 3rd
line – this test is expensive and should
only be done in patients with at least 2
years exposure to a PI and objective
evidence of good adherence.
Application for 3rd line using the standard
motivation form is required (available from
[email protected]) – the regimen will
be determined by an Expert Committee
based on the pattern of resistant mutations
and the prior history of antiretroviral
exposure.
ix
Assessment of renal function in HIV-infected patients
LoE:III
It is important to monitor the eGFR in patients on TDF.
As far as possible, avoid combining potentially nephrotoxic medicines such
x
as TDF, aminoglycosides, amphotericin B and NSAIDs.
LoE:III
More frequent monitoring may be needed in malnourished patients as the
eGFR may be overestimated in this group.
LoE:III
Currently available ARV FDC preparations on contract circular:

ABC 600 mg + 3TC 300 mg

FTC 200 mg + TDF 300 mg

AZT 300 mg + 3TC 150 mg
xi
LoE:III

TDF 300 mg + FTC 200 mg + EFV 600 mg
2015
10.3
CHAPTER 10
HIV AND AIDS
DOSING OF ART
ART: DOSING AND IMPORTANT ADVERSE EFFECTS
Generic
name
Tenofovir
(TDF)
Class
NRTI
Usual
dose
300 mg
daily
Renal adjusted
dose
Avoid in renal
impairment
Important adverse drug
reactions and timing
»
»
»
Abacavir
(ABC)
NRTI
600 mg
daily
Dose adjustment
not required
»
»
Zidovudine
(AZT)
NRTI
300 mg
12 hourly
CrCl <10mL/min:
300 mg daily
»
»
»
»
»
Lamivudine
(3TC)
Emtricitabine
(FTC)
NRTI
NRTI
300 mg
daily
(or
150 mg 12
hourly)
200 mg
daily
CrCl 10-50mL/min:
150 mg daily
CrCl <10mL/min:
50 mg daily
CrCl 30-50 mL/min:
200 mg every 2
days
»
»
»
»
»
Palmar hyperpigmentation.
Hyperlactataemia /
steatohepatitis (very low risk months).
»
Rash and/or Hepatitis (1 week
to 3 months).
*Avoid in women with a CD4
count >250 cells/mm3 and men
with a CD4 count >400
cells/mm3 initiating ART due to
increased risk of rash
associated hepatitis.
Central nervous system
symptoms (vivid dreams,
problems with concentration,
confusion, mood disturbance,
CrCl 15-29mL/min:
200 mg every 3
days
Nevirapine
(NVP)
NNRTI
200 mg
daily for 14
days
then
200 mg
12 hourly
Efavirenz
(EFV)
NNRTI
600 mg
at night
2015
CrCl <15mL/min:
200 mg every 4
days
Dose adjustment
not required
Dose adjustment
not required
Renal failure (weeks to months).
Reduced bone mineral density
(months).
Hyperlactataemia/
steatohepatitis (very low risk months).
Hypersensitivity reaction (1 to 6
weeks) fever, rash,
constitutional symptoms,
gastrointestinal symptoms and
respiratory symptoms.
Hyperlactataemia/
steatohepatitis (very low risk months).
Anaemia, neutropaenia (weeks
to months).
Gastro-intestinal upset.
Headache.
Myopathy.
Hyperlactataemia /
steatohepatitis (medium risk months).
Lipoatrophy (months).
Anaemia due to pure red cell
aplasia (very rare).
Hyperlactataemia /
steatohepatitis (very low risk months).
»
10.4
CHAPTER 10
Lopinavir/
ritonavir
(LPV/r)
Boosted
PI
Atazanavir/
ritonavir
(ATV/r)
Boosted
PI
HIV AND AIDS
400/100
mg
12hourly
OR
800/200
mg daily
(only if PInaïve)
300 mg
with
ritonavir
100 mg
daily
Dose adjustment
not required
Dose adjustment
not required
»
»
»
»
»
»
»
psychosis).
Rash (1 to 6 weeks).
Hepatitis (weeks to months)
Gynaecomastia.
Gastrointestinal upset.
Dyslipidaemia (weeks).
Rash and/or Hepatitis (1 to 6
weeks).
Unconjugated
hyperbilirubinaemia (common,
but benign as there is no
associated hepatitis).
Dyslipidaemia (low risk).
Hepatitis (1 to 6 weeks).
Renal stones (not common).
»
»
»
The time-onset information with respect to adverse drug reactions (ADRs)
serves as an estimate. Patients may present with ADRs with the onset
deviating from that indicated in the table.
xii
LoE:III
Important drug interactions to consider in patients treated for TB with
rifampicin regimens:
» Efavirenz is not affected and no dose adjustment is needed.
» Nevirapine concentrations are modestly reduced. If efavirenz is contraindicated nevirapine can be used, but the lead-in dose of nevirapine must
xiii
be omitted.
LoE:III
» Lopinavir concentrations are markedly reduced.
The dose should be doubled slowly (increase to 3 tablets 12 hourly after
a week, then 4 tablets 12 hourly after another week, with monthly ALT
monitoring).
» In patients on atazanavir or darunavir requiring treatment for TB,
rifampicin is contraindicated. Instead use:

Rifabutin, oral, 150 mg 3 times a week.
xiv
LoE:III
MONITORING FOR SAFETY
At HIV Diagnosis
» Confirm HIV positive result with antibody test.
» WHO staging.
» Check CD4 count.
- CD4 <100 cells/mm3: Check cryptococcus antigen (If
symptomatic, perform LP).
CD4 <200 cells/mm3: Fast track for ART initiation, initiate
cotrimoxazole prophylaxis.
- CD4 <350 cells/mm3: Prioritise for ART.
» Screen for pregnancy or ask if planning to conceive.
» Screen for TB using the WHO screening questionnaire (any one
of cough, fever, night sweats, or weight loss).
-
2015
10.5
CHAPTER 10
Prior to initiating
ART
HIV AND AIDS
» Check creatinine if requires TDF (avoid TDF if eGFR/CrCl
<50 ml/min).
» Check FBC if requires AZT (avoid AZT if Hb <8 g/dl).
» Check ALT if requires NVP (avoid NVP if underlying liver
disease or HBsAg positive).
» Check HBsAg (If positive, TDF and FTC should form part of
the regimen).
» Urine dipstix for glycosuria and proteinuria.
» VL at 6 and 12 months after initiating ART and every 12
On ART
months thereafter.
» CD4 at 12 months after initiating ART*.
» Creatinine at 3, 6 and 12 months after initiation, and every
12 months thereafter if on TDF.
» Urine dipstix at 3, 6 and 12 months after initiation, and every
12 months thereafter if on TDF.
» FBC at 3 and 6 months after initiating AZT, then every 12
months.
» ALT if rash or features of hepatitis develops on NVP.
» Fasting cholesterol and triglycerides at 3 months after
initiating LPV/r.
*Stop CD4 count monitoring when >200 cells/mm 3 and
virologically suppressed. However, if virological or clinical
failure occurs, then a CD4 count should be repeated as
cotrimoxazole may need to be commenced/recommenced.
xv
LoE:III
10.1.1
HIV IN KIDNEY DISEASE
B20/ N18
DESCRIPTION
Various forms of kidney disorders are described among patients who are HIVinfected.
Early detection of kidney disease is important in order to implement
interventions that may slow kidney disease progression, and for adjusting the
dose of relevant medicines.
Screening for kidney disease should be done in all patients at time of HIV
diagnosis.
Patients at high risk or susceptible for HIV renal disease includes:
3
» CD4 count < 200 cells/mm .
» History of nephrotoxic medications.
» Comorbidity such as diabetes mellitus, hypertension, or hepatitis C virus
co-infection.
Screening for renal disease in HIV
» Tests should include:
 Urine dipstix for haematuria and proteinuria.
 Serum creatinine and eGFR.
2015
10.6
CHAPTER 10
»
»
HIV AND AIDS
If there is no evidence of kidney disease at the initial evaluation, and the
patient is receiving TDF, screening should be repeated at months 3, 6
and 12 after initiation, and then annually.
For patients receiving TDF, monitor creatinine on initiation and at months
3, 6, 12 and then annually.
Dose adjustment of ART in renal impairment: Refer to table: Dosing of ART
for renal adjusted doses.
10.1.2
MANAGEMENT OF SELECTED ANTIRETROVIRAL
ADVERSE DRUG REACTIONS
Dyslipidaemia
Certain antiretroviral medication, particularly the protease inhibitors, can cause
dyslipidaemia. Fasting lipid levels should be done 3 months after starting
protease inhibitors. LPV/r is associated with a higher risk of dyslipidaemia than
ATV/r.
Patients on LPV/r:
» who develop triglycerides >10 mmol/L; or
» have a total cholesterol >6 mmol/L with a high risk (>20% risk of
developing a CVS event in 10 years) should switch to ATV/r and repeat
the fasting lipid profile in three months.
Patients with persistent dyslipidaemia despite switching to ATV/r, qualify for
lipid lowering therapy. Criteria for initiating lipid lowering therapy are the
same as for HIV seronegative patients. (See section 3.1: Ischaemic heart
disease and atherosclerosis, prevention).
Many statins (including simvastatin) cannot be used with protease inhibitors,
as protease inhibitors inhibit the metabolism of the statin resulting in
extremely high blood levels.
Patients, who fail to respond to lifestyle modification and have
hypertriglyceridemia, treat with a fibric acid derivative, e.g.:

Bezafibrate, oral, 400 mg at night.
OR
If LDL cholesterol is raised (See section 3.1: Ischaemic heart disease and
atherosclerosis, prevention):

Atorvastatin, oral, 10 mg daily.
Anaemia and neutropenia
AZT causes macrocytosis and can cause anaemia and neutropenia (but
note that it does not cause thrombocytopenia). AZT does not need to be
stopped with mild anaemia and/or neutropenia, but must be stopped and
replaced with an alternative medication if:
» anaemia is symptomatic,
» anaemia is severe (Hb below 8.0 g/dL), or
9
» the neutrophil count is below 0.75 × 10 /L.
2015
10.7
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Lamivudine can cause a red cell aplasia, but this is rare.
Hypersensitivity
Note that pre-existing dermatological conditions (especially papulopruritic
eruptions and acne) may worsen after commencing ART due to immune
reconstitution inflammatory syndrome (see section 10.1.2: Management of
selected antiretroviral adverse drug reactions) – this is not a hypersensitivity
reaction and ART should be continued.
Hypersensitivity rashes occur commonly in the 8 week period after starting
NVP or EFV. NNRTI-associated rashes can be severe and life-threatening,
especially with nevirapine. If a rash develops on NVP an ALT should be
requested urgently. Other drugs, notably co-trimoxazole, can also cause
cutaneous hypersensitivity.
If any of the following features are present or develop then NVP or EFV must
be permanently discontinued:
»
Blistering – if more than 30% of the skin surface is involved this is
called Toxic Epidermal Necrolysis, and requires admission.
»
Lesions affecting mucous membranes (mouth, eyes, or genitals) – this
is called Stevens-Johnson Syndrome, and requires admission
»
Fever.
»
Features of hepatitis (with nevirapine) – either ALT > 5 times the upper
limit of normal or symptomatic hepatitis with deranged liver function tests.
Note that the hepatitis usually starts a week or two after the onset of the
rash.
With mild rashes NVP and EFV can be continued with careful observation
and the rash will often subside. If mild rashes occur on NVP during the dose
lead-in phase (200 mg daily) do not increase the dose to 200 mg 12 hourly
until the rash improves.
If rash worsens or does not improve within a week discontinue EFV or NVP.
If NVP has been stopped due to cutaneous hypersensitivity then EFV can be
substituted provided that the rash has settled and that the reaction was not
life-threatening (either Stevens-Johnson Syndrome or Toxic Epidermal
Necrolysis). If the reaction was life-threatening then a protease inhibitor, e.g.
LPV/r, should be substituted.
ABC can cause a rash as part of a systemic hypersensitivity reaction, which
is confined to people who are HLA-B*5701 positive.
xvi
LoE:III
Hyperlactataemia
Symptomatic hyperlactataemia occurs due to mitochondrial toxicity of
NRTIs. Check for acidosis in such patients.
The estimated risk of lactate elevation differs among the NRTIs as follows:
stavudine > zidovudine > lamivudine or tenofovir or emtricitabine
2015
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HIV AND AIDS
Risk factors for hyperlactataemia include:
» females,
» obesity,
» prolonged use of NRTIs (> 3 months), or
» development of NRTI-induced peripheral neuropathy or fatty liver.
Clinical symptoms of hyperlactataemia are non-specific and may include:
»
nausea
»
vomiting
»
abdominal pain
»
weight loss
»
malaise
»
tachycardia
»
liver dysfunction (due to steatosis)
A high index of suspicion is necessary. Send blood for lactate levels (check
with your local laboratory for specimen requirements for lactate). Alternatively,
point of care finger prick lactate monitoring can be done. Check the serum
bicarbonate level.
Patients with mild hyperlactataemia (lactate 2.5–5 mmol/L):
Therapy should be altered by selecting NRTIs that are less associated with
hyperlactataemia e.g. TDF and ABC.
Monitor serial lactate measurements (initially weekly) until the lactate has
returned to within the normal range.
Note: The resolution of hyperlactataemia may take 3 months or more.
Patients with lactate levels > 5 mmol/L:
Stop the NRTIs.
st
If the patient is on a 1 line regimen, continue the EFV or NVP and add LPV/r.
nd
If the patient is on the 2 line regimen, continue with LPV/r alone.
Note: Many patients will remain with a suppressed viral load when treated
with a boosted protease inhibitor only.
» If severe acidosis was present (serum bicarbonate < 15 mmol/L) NRTIs
should probably not be used again.
» In cases where acidosis was absent or not severe, TDF and 3TC (or FTC)
or ABC could be introduced once symptoms have resolved with serial
lactate monitoring as above. If the patient is on a first line regimen then the
LPV/r can be stopped when the TDF and 3TC have been added and is
tolerated.
If there is acidosis then admission to a high care unit is recommended.
Lactic acidosis carries a poor prognosis. Treatment is largely supportive. It is
essential to exclude other causes of lactic acidosis, especially sepsis. High
dose vitamin B, especially riboflavin and thiamine, may have a role in therapy.
Hepatotoxicity
All currently available antiretrovirals are potentially hepatotoxic. The
NNRTIs, especially nevirapine, have the highest risk. NRTIs uncommonly
cause acute hepatitis, but may result in steatohepatitis after prolonged use,
which manifests with mildly elevated liver enzymes, affecting GGT (glutaryl
2015
10.9
CHAPTER 10
HIV AND AIDS
transferase) and alkaline phosphatase more than the transaminases, and
ALT more than AST. Patients on atazanavir may develop jaundice due an
unconjugated hyperbilirubinaemia, which is not accompanied by liver injury.
This is a cosmetic issue and the atazanavir can be substituted if the patient
is unable to tolerate the jaundice. However, all protease inhibitors can cause
hepatitis, so it is important to exclude this in patients developing jaundice on
ATV/r.
Other potentially hepatotoxic medicines prescribed to in HIV-infected
patients include anti-tuberculous therapy, fluconazole and co-trimoxazole.
Co-trimoxazole, co-amoxiclav and macrolides tend to cause cholestatic
hepatitis that may take months to resolve.
The exclusion of viral hepatitis is important in the work-up of drug-induced
liver injury (DILI). Testing for hepatitis A, B and C should be undertaken.
Hepatitis B is common and flares of viral hepatitis may occur after ART
initiation. Furthermore, life threatening flares may occur when antiretrovirals
that are also active against hepatitis B (TDF, 3TC and FTC) are withdrawn.
Other potential causes include disseminated TB, IRIS, alcohol, alternative
remedies, fatty liver, sepsis and HIV cholangiopathy.
Investigations:
» Request an ALT.
» Request viral hepatitis screen, full liver function tests and INR in
patients if ALT > 5 x upper limit of normal (ULN) and/or jaundice and/or
symptoms of hepatitis are present.
» Perform a liver ultrasound if GGT or ALP are significantly elevated or if
conjugated bilirubin is elevated, to exclude:
- Extrahepatic biliary obstruction.
- Fatty liver due to NRTIs (especially stavudine and didanosine).
- Disseminated TB.
Management:
Upper Limit of
Normal (ULN)
ALT
<2.5 x
2.5 – 5 x
>5x
ULN
ULN
ULN
Repeat in
Repeat in
Stop
2 weeks
1 week
ART
Isolated
Repeat in
Stop ART
Stop
Hyperbilirubinaemia 1 week
ART
*Stop the relevant medicines at lower levels if symptoms of hepatitis (right
upper quadrant pain, nausea / vomiting) or jaundice are present.
If the patient is on an NNRTI-based regimen, stop the NNRTI first and the
NRTIs after 7 days unless the hepatitis is severe, in which case stop all
medicines at once. If the patient is on a PI-based regimen, stop all
medicines at once. Monitor the ALT twice weekly and restart ART once the
ALT has settled to < 2.5 x ULN and the bilirubin has normalised.
2015
10.10
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HIV AND AIDS
Restart and substitute ART as follows:
» If the hepatitis occurred on nevirapine, substitute with efavirenz.
» If the hepatitis occurred on efavirenz, substitute with a boosted PI
(efavirenz may be rechallenged in cases of mild hepatitis).
» If hepatitis occurred on PI, substitute with an alternative PI.
» NRTI fatty liver – safer NRTI combination (TDF, ABC, 3TC, FTC).
Monitor the ALT twice weekly for the first 2 weeks and then once weekly
until 4 weeks.
Hepatitis in patients on ART and anti-tuberculosis therapy
Drug-induced liver injury (DILI) is a known adverse effect of anti-tuberculosis
therapy and ART, and is a common problem in HIV/TB co-infected patients.
First-line TB medicines associated with DILI include isoniazid (INH),
rifampicin (RIF) and pyrazinamide (PZA). Anti-tuberculosis therapy
commonly causes transient, mild, asymptomatic elevations in serum
aminotransferase levels not requiring discontinuation of therapy.
If hepatitis develops, as defined above, stop all antiretrovirals (if on a
NNRTI-based regimen the NRTIs should be continued for a week), cotrimoxazole and all potentially hepatotoxic TB medicines (isoniazid,
rifampicin and pyrazinamide).
TB immune reconstitution inflammatory syndrome (TB-IRIS) should be
considered in the differential diagnosis (see section 10.1.2: Management of
selected antiretroviral adverse drug reactions). This condition presents
shortly after ART initiation in patients with TB. The GGT and ALP are
elevated to a greater degree than the transaminases. Mild jaundice with a
conjugated hyperbilirubinaemia and tender hepatosplenomegaly may be
present.
Investigations:
» Request an ALT.
» Request viral hepatitis screen, full liver function tests and INR in
patients if ALT > 5 x ULN and/or jaundice and/or symptoms of hepatitis
are present.
» Perform a liver ultrasound if GGT or ALP are significantly elevated or if
conjugated bilirubin is elevated, to exclude extrahepatic biliary
obstruction.
» Reassess the grounds for TB diagnosis.
» Check if patient is on intensive or continuation phase of TB treatment.
Management:
» Stop TB therapy and initiate background TB therapy and continue
throughout rechallenge:

Amikacin, IV, 15 mg/kg daily.

Moxifloxacin, oral, 400 mg daily or levofloxacin 750 - 1000 mg daily.

Ethambutol, oral, 800 - 1200 mg daily.
2015
10.11
CHAPTER 10
»
»
»
»
HIV AND AIDS
Stop co-trimoxazole prophylaxis and do not rechallenge.
Stop ART as described above.
Repeat ALT and bilirubin in 2 days (inpatient) or 7 days (outpatient).
When ALT is <100 IU/L and total bilirubin is normal, start TB medicine
rechallenge as follows:
Day 1:
Day 3:
Day 4–6:
2015
 Rifampicin, oral 600 mg daily.
o
If < 60 kg: rifampicin, oral 450 mg daily.
» Check ALT.
ADD
 Isoniazid, oral 300 mg daily.
Day 7:
»
Check ALT.
Day 8:
»
Day 10:
»
»
Consider a pyrazinamide rechallenge (in cases of TB
meningitis
or
intolerance/resistance
to
other
medicines).

Pyrazinamide, oral 25 mg/kg daily.
Check ALT.
Thereafter, monitor ALT twice weekly for the first 3
weeks, then every two weeks for a month, then
monthly until 3 months.

Restart ART 2 weeks after completing rechallenge
of TB therapy:
o If DILI developed on NVP, then rechallenge
with EFV after TB medicine rechallenge
o If DILI developed on EFV, then start a PIbased regimen with lopinavir/ritonavir (with
dose adjustment if receiving rifampicin).
o Monitor ALT every 2 weeks for 2 months after
ART rechallenge.
10.12
CHAPTER 10
HIV AND AIDS
Duration of therapy following successful rechallenge
(A) DILI occurred during the intensive phase
Pyrazinamide not
rechallenged/ not
tolerated
Rifampicin not
tolerated
Isoniazid not
tolerated
Stop moxifloxacin*
Stop amikacin
Continue isoniazid,
rifampicin and
ethambutol
Continue amikacin (for 2
months), pyrazinamide,
moxifloxacin*, isoniazid
and ethambutol
Stop amikacin and
continue
moxifloxacin*,
rifampicin,
ethambutol and
pyrazinamide
For 9 months
at normal doses
For 18 months
For 6 months
at normal doses
at normal doses
(B) DILI occurred during the continuation phase
Rifampicin not
tolerated
Isoniazid not
tolerated
Moxifloxacin*,
isoniazid and
ethambutol
Stop amikacin and
continue
moxifloxacin*,
rifampicin and
ethambutol
For 18 months
For 6 months
*at normal doses*
*at normal doses*
*or levofloxacin
xvii
LoE:III
2015
10.13
CHAPTER 10
10.1.3
HIV AND AIDS
IMMUNE RECONSTITUTION INFLAMMATORY
SYNDROME (IRIS)
D89.3
DESCRIPTION
IRIS occurs when improving immune function unmasks a previously occult
opportunistic disease, which has an unusual inflammatory presentation (this
is called “unmasking IRIS”), or causes paradoxical deterioration of an
existing opportunistic disease (this is called “paradoxical IRIS”). IRIS is more
common in patients with advanced HIV disease, particularly those with
3
a CD4 count <100 cells/mm . IRIS nearly always presents during the first 3
months of ART, with the median time of onset being about two weeks. The
diagnosis of paradoxical IRIS is often difficult as new opportunistic diseases
or drug resistance of the organism causing the opportunistic infection need
to be excluded.
TB is the commonest opportunistic disease involved in IRIS reactions in
South Africa. About a third of patients starting ART while on treatment for
tuberculosis will experience paradoxical IRIS, presenting as recurrence of
their TB symptoms/signs, or worsening, or new manifestations. The
commonest presentation is with enlarging lymph nodes, often with extensive
caseous necrosis. In addition, lung infiltrates or effusions may worsen or
develop. It is important to exclude multi-drug resistance in all patients
suspected with paradoxical TB IRIS.
Other common IRIS manifestations include:
» Inflammatory reactions to skin diseases, especially acne and Kaposi’s
sarcoma.
» Worsening cryptococcal meningitis.
» Flares of hepatitis B or C.
GENERAL MEASURES
Counseling is important to ensure that the patient understands that IRIS
does not mean failure of ART.
Management of IRIS is mainly symptomatic, e.g. aspiration of TB lymph
nodes or effusions.
Continue ART and therapy for the opportunistic infection.
MEDICINE TREATMENT
For pain and fever:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
OR

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
2015
10.14
CHAPTER 10
HIV AND AIDS
For severe IRIS manifestations (e.g. compression of major structures by
enlarging lymph nodes, expanding CNS tuberculomata, worsening meningitis):

Prednisone, oral, 1.5 mg/kg daily for 2 weeks.
o Then 0.75 mg/kg daily for 2 weeks.
Note: Steroids should not be used in patients with Kaposi sarcoma.
10.2
OPPORTUNISTIC DISEASES
10.2.1 ISONIAZID PREVENTIVE THERAPY (IPT)
Z79.2
TB occurs more commonly in HIV-infected patients. IPT is an effective
intervention for reducing the incidence of TB in HIV-infected patients.
Eligibility
All HIV-infected patients, irrespective of CD4 count and ART status.
Exclusions
» Suspected or confirmed TB
» HIV-infected, Tuberculin Skin Test (TST) negative, Pre-ART
» Liver Disease
» Peripheral neuropathy
» Alcohol abusers
» Previous MDR- or XDR-TB
Note:
» TB must be excluded prior to initiating IPT by screening for the following:
- Cough (any duration)
- Weight loss
- Fever
- Night sweats
» IPT should not be initiated in patients if any of the above is present.
These patients require further investigation for active TB.
Duration of IPT
Pre-ART
On ART
TST POSITIVE
36 months
If patient becomes
eligible for ART
while on IPT,
initiate ART and
continue IPT.
36 months
TST NEGATIVE
not indicated
TST NOT AVAILABLE
6 months
12 months
12 months
MEDICINE TREATMENT

Isoniazid, oral 5 mg/kg/day (maximum 300 mg daily).
AND

Pyridoxine, oral 25 mg daily.
2015
xviii
LoE:I
10.15
CHAPTER 10
10.2.2
HIV AND AIDS
OPPURTUNISTIC INFECTION PROPHYLAXIS, WITH
COTRIMOXAZOLE
Z29.2
DESCRIPTION
Primary prophylaxis reduces the probability of developing many infections,
e.g.:
» Pneumocystis pneumonia
» bacteraemia
» toxoplasmosis
» isosporiasis
» bacterial pneumonia
Indications for primary prophylaxis:
» WHO Clinical stage II, III or IV.
3
» CD4 count < 200 cells/mm .
MEDICINE TREATMENT
Prophylaxis

Cotrimoxazole, oral, 160/800 daily.
xix
LoE:I
3
Note: Once the CD4 > 200 cells/mm for longer than 6 months, discontinue
3
prophylaxis. If the CD4 count was > 200 cells/mm when cotrimoxazole was
commenced (e.g. patients with TB) continue for 6 months.
10.2.3
CANDIDIASIS OF OESOPHAGUS/TRACHEA/BRONCHI
B20.4
DESCRIPTION
Mucosal candidiasis involving oesophagus/trachea/bronchi is AIDS-defining
(WHO clinical stage 4). Oesophagitis is by far the commonest manifestation.
Clinical features: symptoms of pain or difficulty on swallowing. Oral thrush is
present in most patients.
GENERAL MEASURES
Maintain adequate hydration.
MEDICINE TREATMENT

Fluconazole, IV/oral, 200 mg daily for 14 days.
o The usual route is oral, but give IV if patient unable to swallow or is
vomiting.
o An early relapse should be treated with a 4-week course of
fluconazole as above.
Note: Fluconazole prophylaxis for candidiasis is discouraged.
2015
10.16
CHAPTER 10
10.2.4
HIV AND AIDS
CRYPTOCOCCOSIS
10.2.4.1 ASYMPTOMATIC CRYPTOCOCCOSIS, CRAG
POSITIVE
B45.1
DESCRIPTION
3
All ART-naïve patients with CD4 < 100 cells/mm should have cryptococcal
antigen (CrAg) test done on serum (unless they had a diagnosis of
cryptococcal infection). The treatment of patients who are CrAg positive
and asymptomatic of meningitis is outlined below.
xx
LoE:III
MEDICINE TREATMENT
Induction phase

Fluconazole, oral 800 mg daily for 14 days
Consolidation phase
Follow with:

Fluconazole, oral, 400 mg daily for 8 weeks.
Maintenance phase

Fluconazole, oral, 200 mg daily.
o Continue for at least 1 year provided that the CD4 count increases to
3
> 200 cells/mm on ART. If the CD4 count does not increase
xxi
continue treatment indefinitely.
LoE:III

Commence ART after completion of the induction phase i.e. at 2 weeks.
xxii
LoE:III
2015
10.17
CHAPTER 10
HIV AND AIDS
Adapted from: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN, Karstaedt
AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR, Chiller T,
Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of cryptococcal
meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
2015
10.18
CHAPTER 10
HIV AND AIDS
10.2.4.2 SYMPTOMATIC, NON-MENINGEAL
CRYPTOCOCCOSIS
B45
DESCRIPTION
This refers to patients who are CrAg positive with non-meningeal
cryptococcal disease. Any anatomical site may be involved, but the lungs
are the commonest site.
MEDICINE TREATMENT
Induction phase

Fluconazole, oral 800 mg daily.
AND

Amphotericin B, slow IV infusion, 1 mg/kg daily in dextrose 5 % over 4
hours for 14 days.
o Ensure adequate hydration to minimise nephrotoxicity. (See
Appendix II for preventing, monitoring and management of toxicity).
Consolidation phase
Follow with:

Fluconazole, oral, 400 mg daily for 8 weeks.
Maintenance phase

Fluconazole, oral, 200 mg daily.
o Continue for at least 1 year provided that the CD4 count increases to
3
> 200 cells/mm on ART. If the CD4 count does not increase
continue treatment indefinitely.
xxiii
LoE:III
10.2.4.3. CRYPTOCOCCAL MENINGITIS
B45
DESCRIPTION
Cryptococcal meningitis is the commonest manifestation of disseminated
cryptococcosis in patients with advanced HIV. Severe headache is common
due to raised intracranial pressure.
GENERAL MEASURES
Therapeutic lumbar puncture is indicated to lower pressure in symptomatic
patients and should be done with pressure monitoring. Remove sufficient
CSF (maximum 30 mL) to lower pressure to 50% of the opening pressure
but not less than 20 cm H2O.
Therapeutic lumbar puncture should be done daily until there is clinical
improvement.
2015
10.19
CHAPTER 10
HIV AND AIDS
MEDICINE TREATMENT
Induction phase

Fluconazole, oral 800 mg daily.
AND

Amphotericin B, slow IV infusion, 1 mg/kg daily in dextrose 5 % over 4
hours for 14 days.

Ensure adequate hydration to minimise nephrotoxicity. (See Appendix II
for preventing, monitoring and management of toxicity).
Consolidation phase
Follow with:

Fluconazole, oral, 400 mg daily for 8 weeks.
Maintenance phase

Fluconazole, oral, 200 mg daily.
o Continue for at least 1 year provided that the CD4 count increases to
3
> 200 cells/mm on ART. If the CD4 count does not increase
continue treatment indefinitely.
xxiv
LoE:III

Commence ART 4–6 weeks after starting antifungal
therapy.
xxv
LoE:III
REFERRAL
Specialist or tertiary
»
Focal neurological signs – CT scan required to exclude other pathology
e.g. toxoplasmosis.
»
Persistent raised intracranial pressure despite daily therapeutic lumbar
puncture.
10.2. 5 CRYPTOSPORIDIOSIS DIARRHOEA
B20.8
DESCRIPTION
Chronic diarrhoea due to Cryptosporidium parvum. Disease lasting >4
weeks is AIDS-defining (WHO clinical stage 4).
GENERAL MEASURES
Rehydration with oral rehydration solution (ORS).
MEDICINE TREATMENT
There is no specific antimicrobial therapy for cryptosporidiosis. As with other
opportunistic diseases it responds well to ART.
Antimotility agents are partially effective, e.g.:

Loperamide, oral, 4 mg initially, followed by 2 mg as required up to four
times daily.
2015
10.20
CHAPTER 10
HIV AND AIDS
10.2.6 CYTOMEGALOVIRUS (CMV)
B25
DESCRIPTION
CMV disease outside the reticulo-endothelial system is an AIDS-defining
illness (WHO clinical stage 4).
3
CMV disease is seen in patients with CD4 counts <100 cells/mm .
The commonest manifestations are:
»
retinitis,
»
git ulceration,
»
pneumonitis, and
»
polyradiculitis.
GIT and other organ involvement must be diagnosed on biopsy.
CNS disease must be diagnosed by PCR of CSF.
The diagnosis of CMV retinitis should be confirmed by an ophthalmologist
Note: CMV serology (IgM and IgG), antigenaemia (pp65), or PCR on blood
are not helpful in the diagnosis of CMV disease in HIV-infected adults.
MEDICINE TREATMENT
Valganciclovir is the treatment of choice, but this agent is toxic and
expensive and can only be used by a specialist familiar with its use.
To prevent recurrent disease commence patients on ART as soon as
possible after initiating valganciclovir.
Maintenance therapy is only applicable to CNS disease and retinitis.
Monitor FBC regularly during therapy. Avoid other medicines associated with
bone marrow suppression, particularly zidovudine.
Biopsy-proven GIT disease and pneumonitis

Valganciclovir, oral, 900 mg 12 hourly for the first 3 weeks, if available.
Specialist initiated.
OR
If unable to tolerate oral medication:

Ganciclovir, IV, 5 mg/kg 12 hourly for 14 days, if available. Specialist initiated.
Maintenance treatment is not indicated unless there has been a relapse.
CNS disease
Initial treatment:

Valganciclovir, oral, 900 mg 12 hourly for the first 3 weeks, if available.
Specialist initiated.
OR
If unable to tolerate oral medication:

Ganciclovir, IV, 5 mg/kg 12 hourly for 14 days. Specialist initiated.
Maintenance treatment:
Only patients with a good clinical response should be considered for
maintenance.
2015
10.21
CHAPTER 10
HIV AND AIDS

Valganciclovir, oral, 900 mg daily untilCD4 count rises to > 100
3
cells/mm on ART, if available. Specialist initiated.
xxvi
OR
LoE:III
If unable to tolerate oral medication:
3

Ganciclovir, IV, 5 mg/kg daily until CD4 count rises to > 100 cells/mm
on ART. Specialist initiated.
REFERRAL/CONSULTATION
Specialist or tertiary
All patients.
10.2.7 ISOSPORIASIS
A07.3
DESCRIPTION
Diarrhoea due to Isospora belli. Disease lasting > 4 weeks is AIDS-defining
(WHO clinical stage 4).
GENERAL MEASURES
Rehydration with oral rehydration solution (ORS).
MEDICINE TREATMENT

Cotrimoxazole 80/400 mg, oral, 4 tablets 12 hourly for 10 days.
OR
If allergic to cotrimoxazole:

Ciprofloxacin, oral, 500 mg 12 hourly for 10 days.
Secondary prophylaxis:
Continue for at least 6 months and until CD4 count increases to > 200
3
cells/mm on ART

Cotrimoxazole 80/400, oral, 2 tablets daily.
10.2.8
MYCOBACTERIOSIS – DISSEMINATED NONTUBERCULOUS
B20.0
DESCRIPTION
Disseminated infection due to non-tuberculous mycobacteria, usually
Mycobacterium avium complex.
Diagnosis must be by culture from sterile sources, e.g. blood, tissue or bone
marrow. Note that culture from a single sputum specimen is not adequate to
make the diagnosis as this often reflects colonisation rather than disease.
Non-tuberculous mycobacteria can cause limited pulmonary disease, which
is diagnosed if the sputum culture is positive repeatedly and there is a
worsening pulmonary infiltrate.
Disseminated disease is AIDS-defining (WHO clinical stage 4).
2015
10.22
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HIV AND AIDS
MEDICINE TREATMENT

Azithromycin, oral, 500 mg daily.
AND

Ethambutol, oral, 15–20 mg/kg daily.
xxvii
LoE:II
Treatment can be stopped when treatment has been continued for at least 12
3
months AND the CD4 count has increased to > 100 cells/mm on ART.
10.2.9 PNEUMOCYSTIS PNEUMONIA
B20.6
DESCRIPTION
Interstitial pneumonitis due to Pneumocystis jirovecii (formerly carinii). AIDSdefining illness (WHO clinical stage 4).
MEDICINE TREATMENT
All patients:

Cotrimoxazole 80/400 mg, oral, 6 hourly for 21 days.
o < 60 kg three tablets
o > 60 kg four tablets
Monitor FBC and potassium when on high dose therapy.
OR
If vomiting:

Cotrimoxazole, IV, 6 hourly.
o < 60 kg 240/1200 mg
o > 60 kg 320/ 1600 mg
For hypoxic patients:

Oxygen by face mask or CPAP as necessary.
AND

Prednisone, oral, 80 mg daily for 5 days, then taper over 14 days.
(Refer to page xxvii for an example of a dose reduction regimen).
Cotrimoxazole intolerance and desensitisation
Attempt desensitisation in patients with a history of cotrimoxazole
intolerance, unless this was life-threatening, e.g. Stevens-Johnson
syndrome. See section 4.6: Erythema Multiforme, Stevens Johnson
Syndrome, Toxic Epidermal Necrolysis. Unless rash is severe or associated
with systemic symptoms, continue treatment with careful observation for
deterioration.
Desensitisation should be attempted using cotrimoxazole suspension 240
mg/5ml. Dilute the suspension appropriately and consult with your
pharmacist if necessary. DO NOT administer antihistamines or steroids.
2015
10.23
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HIV AND AIDS
Time (hours)
0
1
2
3
4
5
Cotrimoxazole dose (mL of
240mg/5mL suspension
0.0005
0.005
0.05
0.5
5
Two single strength tablets (each tablet
= 80/400 mg) followed by full dose
Alternatively, in case of intolerance and unsuccessful desensitisation:

Clindamycin, oral, 600 mg 8 hourly for 21 days.
AND

Primaquine, oral, 15 mg daily for 21 days.
o Exclude G6PD deficiency before initiating therapy.
OR
If primaquine is not available, consider:

Clindamycin, oral, 600 mg 8 hourly for 21 days.
AND

Dapsone, oral, 100 mg daily for 21 days.
Secondary prophylaxis
Continue for at least 6 months and until CD4 count increases to > 200
3
cells/mm on ART.

Cotrimoxazole 80/400 mg, oral, 2 tablets daily.
Alternatively, in case of intolerance:

Dapsone, oral, 100 mg daily.
REFERRAL/CONSULTATION
Specialist or tertiary
Intolerance to second line regimen.
10.2.10 CEREBRAL TOXOPLASMOSIS
B20.8
DESCRIPTION
Intracranial space-occupying lesions, with contrast enhancement on
imaging, due to Toxoplasma gondii. AIDS-defining illness (WHO clinical
stage 4).
The diagnosis of toxoplasmosis is very unlikely if either the serum
3
toxoplasma IgG is negative or the CD4 count is > 200 cells/mm .
Diagnosis is confirmed by a clinical response to therapy, which occurs in 7–14
days. CT scan improvement usually occurs within 14–21 days. Interpreting
the response to therapy may be difficult if steroids have been given
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concomitantly. Steroid therapy should only be given for life-threatening perilesional oedema.
MEDICINE TREATMENT

Cotrimoxazole 80/400, oral, 4 tablets 12 hourly for 28 days, followed by
2 tablets 12 hourly for 3 months.
Secondary prophylaxis
Continue for at least 6 months and until CD4 count increases to > 200
3
cells/mm on ART.

Cotrimoxazole 80/400 mg, oral, 2 tablets daily.
See cotrimoxazole desensitisation: Page 10.23.
REFERRAL/CONSULTATION
Specialist or tertiary
Intolerance to cotrimoxazole.
Note: Attempt desensitisation first.
10.3 KAPOSI SARCOMA (KS)
B21.0
DESCRIPTION
Kaposi Sarcoma (KS) is a malignancy of lymphatic endothelial origin
associated with Human Herpes Virus-8, also known as KS Herpes Virus
infection.
KS may involve the skin, oral cavity, lymph nodes or viscera (especially lung
and intestines).
Most patients have multiple lesions.
Lymphoedema is a common complication.
10–20% of cases of visceral KS will have no oral or skin involvement.
KS is an AIDS-defining illness (WHO clinical stage 4).
Although most cases are diagnosed on the typical macroscopic appearance
of skin and oral lesions, biopsy confirmation is necessary for atypical lesions
and if chemotherapy is considered. One important differential diagnosis is
bacillary angiomatosis, which develops more rapidly.
MEDICINE TREATMENT
All patients with KS should be commenced on ART and cotrimoxazole
prophylaxis regardless of CD4 count.
Many patients with limited mucocutaneous KS will have complete resolution
or substantial regression on ART alone.
REFERRAL
Prior to referral, all patients must be started on ART.
» Radiotherapy/intralesional chemotherapy for symptomatic local lesions.
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»
»
HIV AND AIDS
Systemic chemotherapy is indicated in patients with poor prognostic
factors such as:
more than 25 skin lesions,
rapidly progressive disease,
visceral involvement,
extensive oedema, or
“B” symptoms, i.e. fever, night sweats, significant constitutional
symptoms
Failure of KS to respond to ART.
10.4 POST-EXPOSURE PROPHYLAXIS
Z29.2
National HIV Health Care Worker Hotline: 0800 212 506 or 021 406 6782.
10.4.1 POST-EXPOSURE PROPHYLAXIS, OCCUPATIONAL
Z29.2
DESCRIPTION
Antiretroviral therapy may prevent the risk of acquiring HIV following a
significant occupational exposure.
It is essential to document occupational exposures adequately for possible
subsequent compensation.
Other blood borne infections (hepatitis B and C) should also be tested for in
the source patient and appropriate prophylaxis instituted in the case of
hepatitis B.
Assessing the risk of occupational exposures
The risk of acquiring HIV following occupational exposure is determined by the
nature of the exposure and the infectiousness of the source patient. High-risk
exposures involve exposure to a larger quantity of viruses from the source
patient, either due to exposure to larger quantity of blood or because the amount
of virus in the blood is high.
Any one of the following associated with an increased risk of HIV
transmission:
» deep percutaneous sharps injuries
» percutaneous exposure involving a hollow needle that was used in a vein or
artery
» visible blood on the sharp instrument involved in a percutaneous injury
» the source patient has terminal AIDS or is known to have a high viral
load, i.e. > 100 000 copies/mL
In instances when the risk of infection is extremely low or non-existent, postexposure prophylaxis (PEP) is not indicated, as the risks of PEP will far
outweigh the benefits. PEP is NOT indicated when:
» The material the healthcare worker was exposed to is not infectious for
HIV in the occupational setting, e.g. vomitus, urine, faeces or saliva,
2015
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»
»
»
HIV AND AIDS
unless these are visibly blood stained.
The exposure was on intact skin.
The source patient is HIV negative, unless there are clinical features to
suggest seroconversion illness, in which case PEP should be
commenced until further tests are done – consult with a virologist or
infectious diseases specialist.
The healthcare worker is HIV infected, as this person should be
assessed for ART initiation.
PEP REGIMENS
PEP should be commenced as soon as possible after the injury. Do not
delay initiating PEP while awaiting confirmatory test results on the source
patient and health care worker. PEP should be considered up to 72 hours
after exposure and, in exceptional circumstances involving high-risk
exposures, PEP may be considered up to 7 days after exposure.
When PEP is indicated:

Tenofovir, oral, 300 mg daily for 4 weeks (provided baseline eGFR is
>60 mL/min).
and

Emtricitabine, oral, 200 mg daily for 4 weeks.
and

Atazanavir/ritonavir 300/100 mg daily for 4 weeks.
OR

Lopinavir/ritonavir 200/50, oral, 2 tablets 12 hourly for 4 weeks.
If tenofovir is contraindicated or if source patient is known to be failing a
tenofovir based regimen, replace tenofovir and emtricitabine with:

Zidovudine, oral, 300 mg 12 hourly for 4 weeks.
and

Lamivudine, oral, 150 mg 12 hourly for 4 weeks.
PEP is generally not well tolerated. Adverse effects occur in about half of
cases and therapy is discontinued in about a third. The highest rates of
adverse effects occur with 3-drug regimens. Nevirapine must never be used
for PEP as there is a high risk of severe hepatitis when given to people
without HIV infection. Efavirenz is also not recommended as it is very poorly
tolerated in PEP.
Zidovudine often causes nausea and headache. If zidovudine is not
tolerated, switch to tenofovir (check baseline eGFR as above).
Lopinavir/ritonavir often causes diarrhoea. If lopinavir/ritonavir is not
tolerated switch to atazanavir/ritonavir. Atazanavir/ritonavir often causes
unconjugated jaundice, which is benign but may not be tolerated, in which
case switch to lopinavir/ritonavir.
Recommendations for post exposure prophylaxis (PEP) after occupational
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HIV AND AIDS
exposure to infectious material (includes blood, CSF, semen, vaginal
secretions and synovial/pleural/ pericardial/ peritoneal/amniotic fluid) from
HIV seropositive patients are given in the table, below.
PEP for Healthcare worker following HIV exposure:
Exposure
HIV Status of source patient
Negative
Unknown or Positive
Intact skin
no PEP
no PEP
Mucosal splash
or
non-intact skin
or
percutaneous injury
no PEP
3-drug regimen (PI-based)
When the source patient is known to be failing ART, modify the PEP regimen:
» If the patient is on zidovudine or stavudine, use tenofovir.
» If the patient is on tenofovir then use zidovudine.
nd
Patients failing 2 line ART usually have no resistance to protease
inhibitors, so lopinavir/ritonavir should still be effective, but consultation with
a virologist or infectious diseases physician is recommended for advice on
which ARVs to use for PEP in this setting.
PEP for Health Care workers following hepatitis B exposure
HBsAg positive
Vaccination
status
and
antibody
response
status of
HCW
Unvaccinated
or
vaccination
incomplete
 HBIG, IM, 500
units*
 Hep B vaccine
(3 doses at
monthly intervals)
Source patient
HbsAg
negative
 Initiate Hep B
vaccination
(month 0, 1
and 6)
Vaccinated AND No treatment
No treatment
known to have
HBsAb
> 10 units/mL#
Vaccinated AND  HBIG, IM, 500
No treatment
HBsAb
units *
< 10 units/mL
 Repeat Hep B
or
vaccine
level unknown
(3 doses at monthly
intervals)
HBsAg
unknown
 HBIG, IM, 500
units*
 Hep B vaccine
(3 doses at
monthly
intervals)
No treatment
 HBIG, IM, 500
units*
 Repeat Hep B
vaccine
(3 doses at
monthly
intervals)
* HBIG and first dose of vaccine to be given simultaneously, but at different sites.
#
If the delay in obtaining HBsAb results is more than 24 hours initiate treatment as for vaccinated
AND HBsAb < 10 units/mL.
After vaccination ensure the health care worker has a HBsAb > 10 units/mL 1 – 2 months after the
last vaccine dose.
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HIV AND AIDS
Monitoring in occupational exposures
Source
patient
Baseline
Rapid test
PLUS
4th
generation
ELISA
Surface
antigen
HCV
antibody
RPR/
TP
antibody
Exposed health care worker
Baseline
Rapid test
PLUS
4th
generation
ELISA
Surface
antibody*
HCV
antibody*
RPR/TP
antibody*
2 weeks
Creatinine
If TDF part of
PEP
FBC
If AZT part of
PEP
If TDF
part of
PEP
If AZT
part of
PEP
HIV
Hepatitis B
Hepatitis C
Syphilis
6 weeks
4th
generation
ELISA
4 months
4th
generation
ELISA
HCV PCR*
RPR/TP
antibody*
*Only if source patient was positive.
10.4.2 NON
OCCUPATIONAL
POST
EXPOSURE
PROPHYLAXIS,
SEXUAL
ASSAULT
AND
INADVERTENT EXPOSURE
Z29.2
PEP should be offered to rape survivors who present within 72 hours.
Rape survivors who test HIV seropositive must not be given PEP.
Other important aspects of care for the rape survivor should not be forgotten,
i.e. contraception, treatment for sexually transmitted infections, counseling
and forensic specimens.
Emergency contraception after pregnancy is excluded
Do a pregnancy test in all women and female adolescents. Children must be
tested and given Emergency contraception from Breast Tanner Stage III, if
unsure of staging, give Emergency contraception when you detect any
breast development (DO NOT REGARD MENARCHE AS AN INDICATION).

Levonorgestrel oral, 1.5 mg as a single dose as soon as possible after
xxviii
unprotected intercourse.
LoE:III
CAUTION
Tablets must be taken as soon as possible, preferably within 72 hours of
unprotected intercourse and not > 5 days later.
2015
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HIV AND AIDS
An anti-emetic:

Metoclopramide oral, 10 mg 8 hourly as needed.
xxix
LoE:III
STI prophylaxis

Ceftriaxone, IM, 250 mg as a single dose.
o For ceftriaxone IM injection: Dissolve ceftriaxone 250 mg in 0.9 mL
lidocaine 1% without epinephrine (adrenaline).
AND

Azithromycin, oral, 1 g, as a single dose.
AND

Metronidazole, oral, 2 g immediately as a single dose.
xxx
LoE:III
Inadvertent (non-occupational) exposure to infectious material from HIV
sero-positive persons often requires clinical judgement and includes:
» human bites
» sharing of needles during recreational drug use
» consensual sexual exposure, burst condoms
xxxi
» contact sports with blood exposure
LoE:III
Management of inadvertent (non-occupational) HIV exposure is the same as
for occupational HIV exposure. See section 10.4.1 Post-exposure
prophylaxis, occupational.
References:
i
Criteria for starting ART, CD4 < 500: National Department of Health.National consolidated guidelines for the
prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and
adults, 2014.http://www.health.gov.za/
Criteria for starting ART, CD4 < 500: WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and
preventing HIV infection, June 2013.Web annexes: Chapter 7 Clinical guidance across the continuum of care:
antiretroviral therapy guidelines; section 7.1.1: When to start ART in adults and adolescents and GRADE tables.:
http://www.who.int/hiv/pub/guidelines/arv2013/annexes/en/index2.html
ii
Criteria for starting ART, HIV+hepatitis-B co-infection: National Department of Health.National consolidated guidelines
for the prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents
and adults, 2014.http://www.health.gov.za/
iii
Criteria for starting ART, pregnant and breastfeeding women: National Department of Health.National consolidated
guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children,
adolescents and adults, 2014.http://www.health.gov.za/
Criteria for starting ART, pregnant and breastfeeding women: WHO. Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection, June 2013.Web annexes: Chapter 7 Clinical guidance
across the continuum of care: antiretroviral therapy guidelines;Section 7.1.2: When to start ART in pregnant and
breastfeeding women and GRADE tables.http://www.who.int/hiv/pub/guidelines/arv2013/annexes/en/index2.html
iv
Fast tracking: CD4 < 200: National Department of Health.National consolidated guidelines for the prevention of
mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults,
2014.http://www.health.gov.za/
v
Timing of ART initiation (pulmonary TB): Uthman OA, Okwundu C, Gbenga K, Volmink J, Dowdy D, Zumla A,
Nachega JB. Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed
Pulmonary Tuberculosis: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Jul 7;163(1):32-9.
http://www.ncbi.nlm.nih.gov/pubmed/26148280
vi
Timing of ART initiation (tuberculous meningitis): Török ME, Yen NT, Chau TT, Mai NT, Phu NH, Mai PP, Dung NT,
Chau NV, Bang ND, Tien NA, Minh NH, Hien NQ, Thai PV, Dong DT, Anh do TT, Thoa NT, Hai NN, Lan NN,
Lan NT, Quy HT, Dung NH, Hien TT, Chinh NT, Simmons CP, de Jong M, Wolbers M, Farrar JJ. Timing of initiation of
antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clin Infect Dis.
2011 Jun;52(11):1374-83. http://www.ncbi.nlm.nih.gov/pubmed/21596680
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vii
Timing of ART initiation: National Department of Health.National consolidated guidelines for the prevention of motherto-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults, 2014.
http://www.health.gov.za/
viii
Abacavir: Cruciani M, Mengoli C, Malena M, Serpelloni G, Parisi SG, Moyle G, Bosco O. Virological efficacy of
abacavir: systematic review and meta-analysis. J Antimicrob Chemother. 2014 Dec;69(12):3169-80.
http://www.ncbi.nlm.nih.gov/pubmed/25074854
ix
ART Regimens: National Department of Health.National consolidated guidelines for the prevention of mother-to-child
transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults,
2014.http://www.health.gov.za/
ART regimens: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
x
Renal function in HIV infected patients on nephrotoxic medinces: Kenyon C, Wearne N, Burton R, Meintjes G. The
Risks of Concurrent Treatment with Tenofovir and Aminoglycosides in Patients with HIV-Associated Tuberculosis.
South Afr J HIV Med 2011;12(1):43–45. http://www.ncbi.nlm.nih.gov/pubmed/21695064
xi
FDC formulations currently available: Contract circular HP13-2015ARV. http://www.health.gov.za/
xii
Dosing of ART and ADRs: SAMF, 2014.
Dosing of ART and ADRs: National Department of Health.National consolidated guidelines for the prevention of
mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults,
2014.http://www.health.gov.za/
Dosing of ART (renal impairment): Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, Atta MG,
Wools-Kaloustian KK, Pham PA, Bruggeman LA, Lennox JL, Ray PE, Kalayjian RC; HIV Medicine Association of
the Infectious Diseases Society of America. Clinical practice guideline for the management of chronic kidney
disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious
Diseases Society of America. Clin Infect Dis. 2014 Nov 1;59(9):e96-138.
http://www.ncbi.nlm.nih.gov/pubmed/25234519
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Maartens G, Manzini T, Mathe M, Menezes C, Moorhouse M, Moosa Y, Nash J, Orrell C, Pakade Y, Venter F,
Wilson D (expert panel members). Adult antiretroviral therapy guidelines 2014 By the Southern African HIV
Clinicians Society. S Afr J HIV Med 2014;15(4):121-143.
http://www.sahivsoc.org/upload/documents/2014%20Adult%20ART%20Guideline.pdf
xiii
ART-rifampicin drug interaction: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
ART-rifampicin drug interaction: National Department of Health.National consolidated guidelines for the prevention of
mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults,
2014.http://www.health.gov.za/
xiv
Rifabutin: Zhang J, Zhu L, Stonier M, Coumbis J, Xu X, Wu Y, Arikan D, Farajallah A, Bertz R. Determination of
rifabutin dosing regimen when administered in combination with ritonavir-boosted atazanavir. J Antimicrob Chemother.
2011 Sep;66(9):2075-82. http://www.ncbi.nlm.nih.gov/pubmed/21712242
Rifabutin: Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M,
Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily
lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55.
http://www.ncbi.nlm.nih.gov/pubmed/18722869
Rifabutin: Lan NT, Thu NT, Barrail-Tran A, Duc NH, Lan NN, Laureillard D, Lien TT, Borand L, Quillet C, Connolly C,
Lagarde D, Pym A, Lienhardt C, Dung NH, Taburet AM, Harries AD. Randomised pharmacokinetic trial of rifabutin with
lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam. PLoS One. 2014 Jan
22;9(1):e84866. http://www.ncbi.nlm.nih.gov/pubmed/24465443
Rifabutin: CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis [online]. 2013.
www.cdc.gov/tb/TB_HIV_Drugs/default.htm
xv
Urine dipstix: Han TM, Naicker S, Ramdial PK, Assounga AG. A cross-sectional study of HIV-seropositive patients
with varying degrees of proteinuria in South Africa. Kidney Int. 2006 Jun;69(12):2243-50.
http://www.ncbi.nlm.nih.gov/pubmed/16672914
Screen for Cryptococcus antigen: Southern African HIV Clinician’s Society. Guideline for the prevention, diagnosis
and management of cryptococcal meningitis among HIV-infected persons:2013 update. S Afri HIV Med 2013;14(2):7686. http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
xvi
Abacavir: SAMF, 2014.
xvii
Management of drug-induced liver injury: Jong E, Conradie F, Berhanu R, Black A, John MA, Meintjes G, Menezes
C. Consensus Statement: Management of drug-induced liver injury in HIV-positive patients treated for TB. S Afri HIV
Med 2013;14(3): 113-119. http://www.sajhivmed.org.za/index.php/hivmed/article/view/63
xviii
Isoniazid: Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected
persons. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000171. http://www.ncbi.nlm.nih.gov/pubmed/20091503
Isoniazid: Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Shang N, Mosimaneotsile B, Motsamai OI,
Bozeman L, Davis MK, Talbot EA, Moeti TL, Moffat HJ, Kilmarx PH, Castro KG, Wells CD. 6-month versus 36-month
isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind,
placebo-controlled trial. Lancet. 2011 May 7;377(9777):1588-98. http://www.ncbi.nlm.nih.gov/pubmed/21492926
Isoniazid: Rangaka MX, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, van Cutsem G, Wilkinson KA, Goliath R,
Mathee S, Goemaere E, Maartens G. Lancet. 2014 Aug 23;384(9944):682-90.
http://www.ncbi.nlm.nih.gov/pubmed/24835842
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xix
Cotrimoxazole: National Department of Health.National consolidated guidelines for the prevention of mother-to-child
transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults,
2014.http://www.health.gov.za/
Cotrimoxazole: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
Cotrimoxazole: Grimwade K, Swingler, G. Cotrimoxazole prophylaxis for opportunistic infections in adults with HIV.
Cochrane Database Syst Rev. 2003;(3):CD003108. http://www.ncbi.nlm.nih.gov/pubmed/12917946
xx
Fluconazole (CD4 < 100 cells/mm3): Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A,
Kamya MR, Bohjanen PR, Boulware DR. Cost-effectiveness of serum cryptococcal antigen screening to prevent
deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in
resource-limited settings. Clin Infect Dis. 2010 Aug 15;51(4):448-55.
http://www.ncbi.nlm.nih.gov/pubmed/20597693
xxi
Fluconazole: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN, Karstaedt
AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR, Chiller T,
Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of cryptococcal
meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
Fluconazole: Jarvis JN, Harrison TS, Govender N, Lawn SD, Longley N, Bicanic T, Maartens G, Venter F, Bekker LG,
Wood R, Meintjes G. Routine cryptococcal antigen screening for HIV-infected patients with low CD4+ T-lymphocyte
counts--time to implement in South Africa? S Afr Med J. 2011 Apr;101(4):232-4.
http://www.ncbi.nlm.nih.gov/pubmed/21786721
xxii
ART: Makadzange AT, Ndhlovu CE, Takarinda K, Reid M, Kurangwa M, Gona P, Hakim JG. Early versus delayed
initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin
Infect Dis. 2010 Jun 1;50(11):1532-8.http://www.ncbi.nlm.nih.gov/pubmed/20415574
ART: WHO guidelines: Rapid advice: Diagnosis, prevention and management of cryptococcal disease in HIV-infected
adults, adolescents and children. December, 2011. Available at:
http://www.who.int/hiv/pub/cryptococcal_disease2011/en/index.html
ART: Fluconazole: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN,
Karstaedt AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR,
Chiller T, Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of
cryptococcal meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
xxiii
Fluconazole: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN, Karstaedt
AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR, Chiller T,
Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of cryptococcal
meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
Fluconazole: Jarvis JN, Harrison TS, Govender N, Lawn SD, Longley N, Bicanic T, Maartens G, Venter F, Bekker LG,
Wood R, Meintjes G. Routine cryptococcal antigen screening for HIV-infected patients with low CD4+ T-lymphocyte
counts--time to implement in South Africa? S Afr Med J. 2011 Apr;101(4):232-4.
http://www.ncbi.nlm.nih.gov/pubmed/21786721
xxiv
Fluconazole: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN, Karstaedt
AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR, Chiller T,
Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of cryptococcal
meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
Fluconazole: Jarvis JN, Harrison TS, Govender N, Lawn SD, Longley N, Bicanic T, Maartens G, Venter F, Bekker LG,
Wood R, Meintjes G. Routine cryptococcal antigen screening for HIV-infected patients with low CD4+ T-lymphocyte
counts--time to implement in South Africa? S Afr Med J. 2011 Apr;101(4):232-4.
http://www.ncbi.nlm.nih.gov/pubmed/21786721
xxv
ART: Makadzange AT, Ndhlovu CE, Takarinda K, Reid M, Kurangwa M, Gona P, Hakim JG. Early versus delayed
initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin
Infect Dis. 2010 Jun 1;50(11):1532-8.http://www.ncbi.nlm.nih.gov/pubmed/20415574
ART: WHO guidelines: Rapid advice: Diagnosis, prevention and management of cryptococcal disease in HIV-infected
adults, adolescents and children. December, 2011. Available at:
http://www.who.int/hiv/pub/cryptococcal_disease2011/en/index.html
ART: Fluconazole: Govender NP, Meintjes G (Chairpersons), Bicanic T, Dawood H, Harrison TS, Jarvis JN,
Karstaedt AS, Maartens G, McCarthy KM, Rabie H, Variava E, Venter WDF(Expert panel members), Boulware DR,
Chiller T, Meya DB, Scriven J (Reviewers). Guideline for the prevention, diagnosis and management of
cryptococcal meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):76-86.
http://www.sajhivmed.org.za/index.php/hivmed/article/view/82/128
xxvi
Valganciclovir, oral: 1. Martin DF, Sierra-Madero J, Walmsley S, Wolitz RA, Macey K, Georgiou P, Robinson CA,
Stempien MJ; Valganciclovir Study Group. A controlled trial of valganciclovir as induction therapy for cytomegalovirus
retinitis. N Engl J Med. 2002 Apr 11;346(15):1119-26. http://www.ncbi.nlm.nih.gov/pubmed/11948271
Valganciclovir, oral: Brown F, Banken L, Saywell K, Arum I. Pharmacokinetics of valganciclovir and ganciclovir
following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet.
1999 Aug;37(2):167-76. http://www.ncbi.nlm.nih.gov/pubmed/10496303
xxvii
Azithromycin: Dunne M, Fessel J, Kumar P, Dickenson G, Keiser P, Boulos M, Mogyros M, White Jr AC, Cahn P,
O'Connor M, Lewi D, Green S, Tilles J, Hicks C, Bissett J, Schneider MM, Benner R. A randomized, double-blind trial
2015
10.32
CHAPTER 10
HIV AND AIDS
comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients
with human immunodeficiency virus. Clin Infect Dis. 2000 Nov;31(5):1245-52. Erratum in: Clin Infect Dis 2001 May
1;32(9):1386. http://www.ncbi.nlm.nih.gov/pubmed/11073759
Azithromycin: Ward TT, Rimland D, Kauffman C, Huycke M, Evans TG, Heifets L. Randomized, open-label trial of
azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex
bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium.
Clin Infect Dis. 1998 Nov;27(5):1278-85. http://www.ncbi.nlm.nih.gov/pubmed/9827282
xxviii
Levonorgestrel 1.5 mg: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
xxix
Metoclopramide, oral: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
xxx
STI prophylaxis:Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
xxxi
Non-occupational PEP: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
Non-occupational PEP: South African HIV Clinician Society. Post-exposure prophylaxis guidelines. The S A Jr of
HIV Med, Winter 2008.[Online] Available at: http://www.sahivsoc.org/upload/documents/guidelines_nov_2008.pdf
2015
10.33
CHAPTER 11
SURGICAL ANTIBIOTIC PROPHYLAXIS
GENERAL PRINCIPLES
»
»
»
»
»
»
»
»
»
»
Prophylactic antibiotic therapy reduces the risk of surgical site infection.
The need for surgical antibiotic prophylaxis depends on the nature of
the expected wound from the procedure.
Wounds that are expected to be clean (defined as no inflammation
encountered; and the respiratory, alimentary, genital, or uninfected
urinary tracts were not entered) generally do not require antibiotic
prophylaxis, except where the consequences of surgical site infection
could be severe (e.g. joint replacement in orthopaedic surgery).
Antibiotic prophylaxis is indicated for procedures with cleancontaminated wounds (defined as entering the respiratory, alimentary,
genital, or uninfected urinary tracts under controlled conditions; and
i
without unusual contamination).
LoE:III
A course of antibiotic treatment, not antibiotic prophylaxis, is required for
procedures with contaminated wounds (defined as fresh open
accidental wounds, or operations with major breaks in sterile technique),
or dirty or infected wounds (defined as old traumatic wounds with
retained devitalized tissue; and those that involve existing clinical
ii
infection or perforated viscera).
LoE:III
(See chapter 20: Emergencies and injuries for antibiotic
treatment).
Prophylaxis is not recommended for most uncomplicated clean
procedures.
The antibiotic of choice should be active against the pathogens most
likely to be associated with surgical site infections. Specific
epidemiological considerations may alter the choice of agents.
Give prophylaxis < 60 minutes before the first incision, usually at
iii
induction.
LoE:III
If a tourniquet is used at the site of surgery, administer the entire
iv
antibiotic dose before the tourniquet is inflated.
LoE:III
Antibiotic prophylaxis should be used in conjunction with good pre- and
intra-operative infection prevention strategies.
Dosage recommendations:

Cefazolin, IV.
o If < 80 kg: 1g
o If ≥ 80 kg: 2 g.

Metronidazole, IV, 500 mg.

Gentamicin, IV, 6 mg/kg.

Clindamycin, IV, 600 mg.
2015
v
LoE:III
11.1
CHAPTER 11
SURGICAL ANTIBIOTIC PROPHYLAXIS
In most instances a single antibiotic dose prior to the procedure is
sufficient for prophylaxis. Postoperative antimicrobial administration
is not recommended for most surgeries as this selects for
antimicrobial resistance.
vi
LoE:I
» Additional
intra-operative
doses
should
be
»
administered in circumstances of significant blood loss (>1500 mL) in
order to ensure an adequate antimicrobial level until wound closure.
vii
» LoE:III
With prolonged procedures, antibiotics are required to
be re-dosed (i.e. > 4 hours for cefazolin; > 8 hours for metronidazole; >
6 hours for clindamycin and gentamicin).
viii
LoE:III
ANTIBIOTIC PROPHYLAXIS
TYPE OF SURGERY
Orthopaedic surgery
Gastrointestinal surgery
Thoracic surgery
Cardiac surgery
Vascular surgery
(Prophylaxis is not
recommended for other
clean procedures).
2015
ANTIBIOTIC RECOMMENDED
 Cefazolin, IV
 Cefazolin, IV
AND
 Metronidazole,
IV
Primary total hip or total knee
Lower limb
replacement; internal fixation of
amputation.
hip; spinal procedures; open
reduction and internal fixation of
fractures; insertion of prostheses,
screws, plates, etc.
Gastric/ duodenal/ oesophageal
Biliary, colorectal,
hernia repair.
manipulation of
viscera,
appendicectomy,
division of
adhesions,
Exploratory
laparotomy.
Pneumonectomy/
lobectomy.
Coronary artery bypass
surgery/routine cardiac valve
surgery (continue cefazolin, IV, 8
hourly for 24 hours); cardiac
device insertion (pacemaker
implantation).
Vascular reconstruction:
Lower limb
abdominal aorta, groin incision
amputation.
(continue 8 hourly for 24 hours);
AV fistula formation; and ligation of
varicose veins.
11.2
CHAPTER 11
TYPE OF SURGERY
Urology
Plastic and
reconstructive surgery
(Prophylaxis is not
recommended for clean
bone or soft tissue
surgery).
Otorhinolaryngology/
head and neck surgery
(Prophylaxis is not
recommended for other
procedures such as
tonsillectomy, sinus
procedures, etc.).
Obstetrics/
gynaecology
(Prophylaxis is not
recommended for early
suction termination).
Neurosurgery
(Prophylaxis is not
recommended for other
minor clean procedures).
Endoscopic
gastrointestinal
procedures*
(Prophylaxis is not
recommended for all
other procedures, with or
without biopsy).
General Surgery
(Prophylaxis is not
recommended for
uncomplicated clean
procedures or clean
excision procedures i.e.
wound revision, excision
of scar tissue, etc.).
2015
SURGICAL ANTIBIOTIC PROPHYLAXIS
ANTIBIOTIC RECOMMENDED
 Cefazolin, IV
 Cefazolin, IV
AND
 Metronidazole,
IV
Clean procedures with entry into
Clean-contaminated
urinary tract.
procedures.
Craniotomy procedures.
No incision through the
oropharyngeal mucosa.
With incision
through the
oropharyngeal
mucosa.
Caesarean section.
Hysterectomy,
laparotomy
procedures, vaginal
repair.
Craniotomy; CSF shunt/drain;
laminectomy.
Percutaneous endoscopic
Gastrostomy insertion/revision.
Clean contaminated procedures
(mastectomy, node biopsy, etc.),
splenectomy.
11.3
CHAPTER 11
SURGICAL ANTIBIOTIC PROPHYLAXIS
Beta lactam allergies:
Avoid beta-lactam antimicrobials in patients with a history of anaphylaxis,
urticaria, or angioedema after exposure to one of these agents.

Clindamycin, IV.
ADD

Gentamicin, IV for the procedures listed below:
» Gastrointestinal surgery, urology procedures (clean-contaminated), and
obstetric/gynaecological surgery (hysterectomy, laparotomy procedures,
vaginal repair).
Note: Clindamycin has good coverage against Gram positive organisms and
anaerobes, so the addition of metronidazole is unnecessary.
ix
LoE:III
Ophthalmic surgery:

Chloramphenicol 0.5% ophthalmic drops, instil 1 drop 2–4 hourly for 24
hours prior to surgery.
SPECIAL CONSIDERATIONS
»
»
Elective splenectomy patients should be vaccinated at least 14 days
prior to surgery. If not given prior to surgery it is recommended to give it
x
at least 14 days post-splenectomy.
LoE:II
The following vaccines should be administered:
VACCINE
 Polyvalent pneumococcal vaccine,
subcutaneous.
0.5 mL,
 Haemophilus influenza type B, 0.5 mL,
intramuscular.
 Meningococcal polysaccharide vaccine, 0.5 mL,
subcutaneous.
 Influenza vaccine, 0.5 mL, intramuscular.
SCHEDULE
Revaccinate every 5 years.
xi
LoE:II
–
Revaccinate every 5 years.
Revaccinate annually.
xii
LoE:III
PROCESS MEASURES
Measure the percentage of procedures in which antimicrobial prophylaxis
was appropriately provided.
These include:
» Correct type of antibiotic.
» Correct dose.
» Administration of the antibiotic/s within 1 hour before incision.
» Not continuing the antibiotic/s after surgery (except for 24 hours for
cardiac and selected vascular procedures).
2015
11.4
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References
i
Surgical antibiotic prophylaxis: Centers for Disease Control and Prevention. Procedure-associated Module.
Surgical Site Infection (SSI) Event. [Online] [Published April 2015; accessed December 2015]
http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf
ii
Surgical antibiotic prophylaxis: Centers for Disease Control and Prevention. Procedure-associated Module.
Surgical Site Infection (SSI) Event. [Online] [Published April 2015; accessed December 2015]
http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf
iii
Surgical antibiotic prophylaxis (timing): Burke JP. Maximizing appropriate antibiotic prophylaxis for surgical
patients:an update from LDS Hospital, Salt Lake City. Clin Infect Dis. 2001 Sep 1;33 Suppl 2:S78-83.
http://www.ncbi.nlm.nih.gov/pubmed/11486303
Surgical antibiotic prophylaxis (timing): Bratzler DW, Houck PM, Richards C, Steele L, Dellinger EP, Fry DE,
Wright C, Ma A, Carr K, Red L. Use of antimicrobial prophylaxis for major surgery: baseline results from the
National Surgical Infection Prevention Project. Arch Surg. 2005 Feb;140(2):174-82. PubMed PMID: 15724000.
http://www.ncbi.nlm.nih.gov/pubmed/11486303
Surgical antibiotic prophylaxis (timing): van Kasteren ME, Manniën J, Ott A, Kullberg BJ, de Boer AS, Gyssens
IC. Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration
is the most important factor. Clin Infect Dis. 2007 Apr 1;44(7):921-7. http://www.ncbi.nlm.nih.gov/pubmed/17342642
Surgical antibiotic prophylaxis (timing): Koch CG, Li L, Hixson E, Tang A, Gordon S, Longworth D, Phillips S,
Blackstone E, Henderson JM. Is it time to refine? An exploration and simulation of optimal antibiotic timing in
general surgery. J Am Coll Surg. 2013 Oct;217(4):628-35.http://www.ncbi.nlm.nih.gov/pubmed/23849901
iv
Surgical antibiotic prophylaxis (tourniquet): Bratzler DW, Houck PM; Surgical Infection Prevention Guidelines
Writers Workgroup; American Academy of Orthopaedic Surgeons; American Association of Critical Care Nurses;
American Association of Nurse Anesthetists; American College of Surgeons; American College of Osteopathic
Surgeons; American Geriatrics Society; American Society of Anesthesiologists; American Society of Colon and
Rectal Surgeons; American Society of Health-System Pharmacists; American Society of PeriAnesthesia Nurses;
Ascension Health; Association of periOperative Registered Nurses; Association for Professionals in Infection
Control and Epidemiology; Infectious Diseases Society of America; Medical Letter; Premier; Society for Healthcare
Epidemiology of America; Society of Thoracic Surgeons; Surgical Infection Society. Antimicrobial prophylaxis for
surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004 Jun
15;38(12):1706-15. http://www.ncbi.nlm.nih.gov/pubmed/15227616
v
Cefazolin (dose): Chopra T, Zhao JJ, Alangaden G, Wood MH, Kaye KS. Preventing surgical site infections
after bariatric surgery: value of perioperative antibiotic regimens. Expert Rev Pharmacoecon Outcomes Res. 2010
Jun;10(3):317-28. http://www.ncbi.nlm.nih.gov/pubmed/20545596
Cefaxolin (dose): Huttunen R, Karppelin M, Syrjänen J. Obesity and nosocomial infections. J Hosp
Infect. 2013 Sep;85(1):8-16. http://www.ncbi.nlm.nih.gov/pubmed/23920442
vi
Surgical antibiotic prophylaxis (single dose): McDonald M, Grabsch E, Marshall C, Forbes A. Single- versus
multiple-dose antimicrobial prophylaxis for major surgery: a systematic review. Aust N Z J Surg. 1998
Jun;68(6):388-96. http://www.ncbi.nlm.nih.gov/pubmed/9623456
Surgical antibiotic prophylaxis (single dose): Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG,
Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American Society of HealthSystem Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare
Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst
Pharm. 2013 Feb 1;70(3):195-283. http://www.ncbi.nlm.nih.gov/pubmed/23327981
vii
Surgical antibiotic prophylaxis (blood loss > 1500 mL): Bratzler DW, Dellinger EP, Olsen KM, Perl TM,
Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American
Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society
for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J
Health Syst Pharm. 2013 Feb 1;70(3):195-283. http://www.ncbi.nlm.nih.gov/pubmed/23327981
viii
Surgical antibiotic prophylaxis (re-dosing): Ohge H, Takesue Y, Yokoyama T, Murakami Y, Hiyama E,
Yokoyama Y, Kanehiro T, Itaha H, Matsuura Y. An additional dose of cefazolin for intraoperative prophylaxis. Surg
Today. 1999;29(12):1233-6. http://www.ncbi.nlm.nih.gov/pubmed/16039702
ix
Clindamycin: Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano
LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American Society of Health-System Pharmacists; Infectious
Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical
practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013 Feb 1;70(3):195-283.
http://www.ncbi.nlm.nih.gov/pubmed/23327981
x
Immunisation –splenectomy (timing): Shatz DV, Schinsky MF, Pais LB, Romero-Steiner S, Kirton OC, Carlone
GM. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine
at 1 versus 7 versus 14 days after splenectomy. J Trauma.
1998 May;44(5):760-5; discussion 765-6. http://www.ncbi.nlm.nih.gov/pubmed/9603075
Immunisation –splenectomy (timing): Konradsen HB, Rasmussen C, Ejstrud P, Hansen JB. Antibody levels
against Streptococcus pneumoniae and Haemophilus influenzae type b in a population of splenectomized
individuals with varying vaccination status. Epidemiol Infect. 1997 Oct;119(2):167-74.
http://www.ncbi.nlm.nih.gov/pubmed/9363015
xi
Splenectomy: polyvalent pneumococcal vaccine revaccination: Rutherford EJ, Livengood J, Higginbotham M,
Miles WS, Koestner J, Edwards KM, Sharp KW, Morris JA Jr. Efficacy and safety of pneumococcal revaccination
after splenectomy for trauma. J Trauma. 1995 Sep;39(3):448-52. http://www.ncbi.nlm.nih.gov/pubmed/7473907
xii
Vaccines splenectomy: Davies JM, Lewis MP, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH; British
Committee for Standards in Haematology. Review of guidelines for the prevention and treatment of infection in
2015
11.5
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SURGICAL ANTIBIOTIC PROPHYLAXIS
patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in
Haematology by a working party of the Haemato-Oncology task force. Br J Haematol. 2011 Nov;155(3):308-17.
http://www.ncbi.nlm.nih.gov/pubmed/21988145
Vaccines – splenectomy: Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A,
Dhanireddy S, Sung L, Keyserling H, Kang I, Infectious Diseases Society of America. 2013 IDSA clinical practice
guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014 Feb;58(3):e44-100.
http://www.ncbi.nlm.nih.gov/pubmed/24311479
Vaccines – splenectomy: Davidson RN, Wall RA. Prevention and management of infections in patients
without a spleen. Clin Microbiol Infect. 2001 Dec;7(12):657-60. http://www.ncbi.nlm.nih.gov/pubmed/11843905
Vaccines – splenectomy: Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among
post-splenectomy patients. J Infect. 2001 Oct;43(3):182-6. http://www.ncbi.nlm.nih.gov/pubmed/11798256
2015
11.6
CHAPTER 12
ANAESTHESIOLOGY, PAIN AND INTENSIVE
CARE
Anaesthetic and sedative medication may only be administered by medical
practitioners trained and experienced in their use.
Medicines and equipment for resuscitation should be immediately available
whenever general anaesthesia, regional anaesthesia or sedation is
administered.
The following is a list of medicines required for anaesthesia that should be
available at district and regional hospitals.
The doses of the medicines given are those recommended for healthy
adults. Patients who are acutely or chronically sick, or elderly, may
require substantial reductions in the doses given otherwise lifethreatening adverse effects may ensue.
12.1 PREMEDICATION

Lorazepam, 1–2 mg, oral the night before surgery and 1–2 hours
preoperatively
o Use half the dose in elderly.
o Duration of action (10-20 hours).
o Unsuitable for day case surgery.

Midazolam, 7.5mg oral one hour preoperatively.
o Use only in healthy adults < 65 years of age.
o Duration of action 1–4 hours.
o Suitable for day case surgery.
i
LoE:III
12.2 GENERAL ANAESTHESIA
12.2.1 INTRAVENOUS INDUCTION (AND/OR
MAINTENANCE) AGENTS
Inject intravenous induction agents over 30 seconds (> 60 seconds in the
elderly). Titrate the dose to effect. Respiratory depression occurs following
induction of anaesthesia and ventilation should be supported as required.
Propofol is the most widely used IV induction agent but can produce
hypotension. Etomidate or ketamine is preferred in haemodynamically
2015
12.1
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
unstable patients. Thiopentone has a rapid onset and may be preferred for
Caesarean sections.

Propofol, IV, 1.5–2.5 mg/kg.
o 6-12 mg/kg/hour IV infusion for maintenance, if volatile agent use
contraindicated.

Etomidate, IV, 0.3 mg/kg (0.2-0.6 mg/kg)

Ketamine, IV, 1–2 mg/kg.

Thiopental, IV, 3–5 mg/kg.
12.2.2 INHALATION AGENTS
12.2.2.1 INDUCTION
In adults, intravenous induction is preferable. Inhalational induction is
reserved for patients with difficult airways or severe needle phobia.
Use only halothane or sevoflurane (isoflurane is too irritant). Halothane can
cause hepatitis after repeated exposure within 3 months. Halothane
sensitises the heart to catecholamines and may cause cardiac dysrhythmias,
particularly if anaesthesia is too light or the patient hypercarbic.
Sevoflurane is not associated with these problems, has a faster onset and
emergence time.

Halothane, titrated to 4%.
OR

Sevoflurane, titrated to 8%.
ii
LoE:III
12.2.2.2 MAINTENANCE
In spontaneously breathing patients, the dose of volatile agent is titrated to
clinical effect. If a neuromuscular blocking agent has been used, the dose of
the volatile agents must be adequate to prevent awareness. This is about 1
minimum alveolar concentration (MAC), but must be titrated according to
clinical signs of awareness (e.g. tachycardia, hypertension, sweating,
lacrimation).

Isoflurane (MAC = 1.2%).
12.3 MUSCLE RELAXANTS
To facilitate intubation and provide intraoperative muscle relaxation for
surgery. Must not be used if difficult intubation anticipated.
12.3.1 DEPOLARISING MUSCLE RELAXANTS

Suxamethonium, IV, 1–1.5 mg/kg.
2015
12.2
CHAPTER 12
o
o
o
o
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Onset 30–60 seconds.
Duration 5 minutes.
Repeated doses associated with bradycardia and prolonged
neuromuscular block.
Contraindicated in patients at risk for developing suxamthoniuminduced hyperkalaemia, e.g. upper or lower motor neuron defect,
prolonged chemical denervation, direct muscle trauma, tumour or
inflammation, thermal trauma, disuse atrophy, severe infection.
iii
LoE:III
12.3.2 NON-DEPOLARISING MUSCLE RELAXANTS
(NDMR)
Use a nerve stimulator to monitor effect and determine when subsequent
doses (about a fifth of the intubating dose) are required.
Higher doses result in shorter onset times but longer duration of action.

Cisatracurium
o Intubation dose 0.1–0.15 mg/kg.
o Onset 3–5 minutes.
o Duration of action 45–55 minutes.
o Eliminated by Hoffman degradation, therefore can be used in renal
or liver impairment.

Vecuronium
o Intubation dose 0.08–0.1 mg/kg.
iv
o Intubate after 2 minutes.
LoE:III
o Duration 20–30 minutes.
o Eliminated by liver and kidney: avoid in renal and liver impairment.
12.3.3 MUSCLE RELAXATION FOR RAPID SEQUENCE
INTUBATION
Patients at risk of aspiration (e.g. emergency surgery, incomplete gastric
emptying) require a rapid sequence intubation.
An IV induction agent is given through an IV line with fast running fluids,
immediately followed by a rapidly acting muscle relaxant.
Cricoid pressure is applied and then intubation proceeds.
The rapid onset of action enables the time to intubation to be short enough
to avoid mask ventilation, as this can result in gastric insufflation and
aspiration of gastric contents.

Suxamethonium, 1–1.5 mg/kg, IV. (See section 12.3.1: Depolarising
muscle relaxants).
o Preferred agent as, in the event of a failed intubation, it wears off
quickly enabling spontaneous respiration to resume.
o Contraindications to suxamethonium
2015
12.3
CHAPTER 12
-
-
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Congenital and acquired medical conditions associated with
severe,
potentially
lethal
suxamethonium-induced
hyperkalaemia.
v
Malignant hyperthermia.
LoE:I
If suxamethonium is contra-indicated, consider:

Rocuronium, 0.9 mg/kg, IV.
vi
o Duration +/- 60 minutes.
LoE:III
Sub-optimal conditions for intubating and prolonged effect
can be problematic in the event of a difficult or failed intubation and if the
procedure is short.
12.3.4 MEDICINES TO REVERSE MUSCLE RELAXATION
Only administer when the clinical signs of NDMR are wearing off or at least 2
twitches occur using train-of-four on nerve stimulator.
Neostigmine has profound cholinergic effects and, to counteract resultant
profound bradycardia, is administered mixed with an anticholinergic agent,
atropine or glycopyrrolate.
Whilst atropine is effective and can be used for this purpose in otherwise
healthy patients, the onset of neostigmine and duration of action more
closely matches that of glycopyrrolate, so this is the preferred combination
agent for patients who poorly tolerate tachycardia or bradycardia.

Neostigmine, IV, 50 mcg/kg.
vii
LoE:III
WITH EITHER:
 Atropine, IV, 20 mcg/kg (maximum 1.2 mg).
OR
Glycopyrrolate, IV, 10 mcg/kg.
viii
LoE:III
ix
LoE:III
12.4 PERIOPERATIVE ANALGESIA
R52.9
»
»
»
»
The perioperative period includes the preoperative, intraoperative and
post-operative stages of surgery.
Perioperative analgesia should be multi-modal, i.e. use analgesics, where
possible, from different classes to reduce side effects from high doses of
a single agent (e.g. paracetamol, NSAID and a weak/strong opioid) with
either a regional block or wound infiltration with local anaesthetic.
Patients with pain before surgery should be given analgesia
preoperatively.
Paracetamol may be given orally with premedication to prophylactically
reduce perioperative pain.
2015
12.4
CHAPTER 12
»
»
»
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Intraoperatively, analgesics are given intravenously and/or a central
neuraxial or regional local anaesthetic block may be used. The
analgesic effect of these may extend into the early postoperative period.
Postoperatively analgesics are given IV, IM and/or rectally, until the
patient is able to take oral medication. Patients with a functioning block
may not require analgesia until the block wears off but analgesics
should be prescribed in anticipation of this.
Pain severity should be assessed frequently post-operatively (see
Section 12.5.3: Postoperative analgesia ward prescriptions).
12.4.1 PERIOPERATIVE ANALGESICS
12.4.1.1 ORAL ANALGESICS

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
x
AND
LoE:I

Tramadol, oral, 50–100 mg, 6 hourly.
o Avoid in head injury and epilepsy.
o Improved effect when given with paracetamol.
xi
LoE:III
AND

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
Note: Do not administer NSAIDs to patients at risk of hypovolaemia, renal
impairment or gastrointestinal bleeding. Avoid in patients with asthma who
xii
experience bronchospasm with NSAIDs.
LoE:III
12.4.1.2 INTRAVENOUS ANALGESICS

Fentanyl, IV, 1–2 mcg/kg
o Onset ± 3 minutes, duration of action 30–60 minutes. Higher doses
xiii
last longer.
LoE:III

Morphine, IV/IM, 3–5 mg as a single dose then further boluses of 1–2
mg/minute and monitor closely.
o Dilute 10 mg up to 10 mL with sodium chloride 0.9%.
o Total maximum dose: 10 mg.
o Repeat after 4 hours if necessary.
o Monitor response to pain and effects on respiration and BP.
o Onset 5-10 minutes. Duration of action ± 3 hours.
o Histamine release may cause intraoperative hypotension.

Ketamine, IV, 0.15 mg/kg – a subanaesthetic dose given pre-incision
xiv
may reduce persistent post-surgical pain.
LoE:II
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
12.4.2 POSTOPERATIVE PAIN IN THE RECOVERY
ROOM
R52.0
Pain should be assessed on arrival in the recovery room and at regular
intervals postoperatively. Pain Scores should be recorded with other routine
postoperative observations.
A Numeric Rating Scale (NRS) can be used to score pain:
Source: Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, Kvarstein G,
Stubhaug A. Assessment of pain. Br J Anaesth. 2008 Jul;101(1):17-24.
The patient is asked to indicate on the scale the numeric value that best
indicates their pain intensity or verbally if they cannot visualise the scale.
Severe pain (use lower doses if pain less):

Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
o Monitor conscious level and pulse oximetry continuously. Also
monitor respiration, heart rate and BP at 5 minute intervals and for
at least 20 minutes after the last IV morphine bolus.
In patients at high risk for respiratory depression, tramadol may be used
instead of morphine as it causes less respiratory depression (although
respiratory depression may still occur with tramadol).
Tramadol is a weak opioid agonist and increases spinal cord levels of
serotonin and noradrenaline.

Tramadol, IV, 50–100 mg, over 3 minutes (Specialist prescribed).
xv
o Ceiling effect i.e. higher doses do not improve pain
LoE:III
relief.
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In addition to morphine or tramadol, diclofenac may also be given to
supplement analgesia and reduce opioid requirements:

Diclofenac, deep IM, 75 mg 12 hourly, to upper, outer quadrant of
buttock.
12.4.3 POSTOPERATIVE ANALGESIA WARD
PRESCRIPTIONS
Analgesia should be prescribed according to the severity of pain anticipated
from the surgery and the anticipated, appropriate, postoperative route of
administration.
Pain should be assessed at regular intervals on the ward postoperatively. Pain
scores should be recorded with other routine postoperative observations.
12.4.3.1 EXAMPLES OF WARD PRESCRIPTIONS FOR
POSTOPERATIVE ANALGESIA ACCORDING TO
ANTICIPATED PAIN SEVERITY
R52.9
MILD PAIN:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND

NSAIDs, oral, e.g.:

Ibuprofen, oral, 400 mg 8 hourly after meals.
AND
o Tramadol, oral, 50–100 mg, 6 hourly. Avoid in head injury and
epilepsy.
o Improved effect when given with paracetamol.
MODERATE PAIN:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND

NSAIDs, oral, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
AND

Tramadol, oral, 50–100 mg, 6 hourly.
o Avoid in head injury and epilepsy.
o Improved effect when given with paracetamol.
2015
12.7
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
OR
Morphine, IM, 0.1–0.2 mg/kg, 4 hourly or IV via a patient controlled
analgesia device (see below).
SEVERE PAIN:

Morphine, IM, 0.1–0.2 mg/kg, 4 hourly or IV via a PCA device.
AND

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND

NSAID, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
xvi
LoE:III
Note:
Patient controlled analgesia
If a device is available that will administer patient controlled analgesia:

Morphine, IV, in boluses of 1 mg every 6-10 minutes, with a maximum
dose of 0.1–0.2 mg/kg 4 hourly.
o In the elderly and frail, the dose of morphine should be reduced and
the dosage interval increased.
xvii
LoE:I
If unable to take oral medication, stop oral ibuprofen and use:
 Diclofenac, deep IM, 75 mg 12 hourly, to upper, outer quadrant of
buttock.
12.5 INTRAVENOUS FLUIDS
The following IV fluids should be available for perioperative fluid replacement
and maintenance therapy.
12.5.1 CRYSTALLOIDS

Ringer Lactate, IV.
Most commonly used crystalloid for perioperative fluid maintenance:

Sodium chloride 0.9%, IV.
Higher sodium content than Ringer lactate. Indicated if perioperative risk of
hyponatraemia e.g. transurethral resection of prostate.
xviii
LoE:III
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
12.6 MEDICINES TO TREAT COMPLICATIONS OF
ANAESTHESIA
12.6.1 MALIGNANT HYPERTHERMIA
T88.3

Dantrolene IV, 2 mg/kg as a single dose.
o Repeat doses until cardiac and respiratory symptoms stabilise.
xix
o Up to 10 mg/kg may be required.
LoE:III
12.6.2 LOCAL ANAESTHETIC TOXICITY
T41.3
Airway management:

Ventilate with 100% oxygen.
Seizure suppression:

Diazepam, IV, 10 mg.
Cardiopulmonary resuscitation may be required.

Reduce individual adrenaline (epinephrine) doses to < 1 mcg/kg.
xx
LoE:III

Lipid emulsion (20%), IV, 1.5 mL/kg over 1 min, then continuous
infusion 0.25 mL/kg/min.
o Repeat bolus 1–2 times for persistent cardiovascular collapse.
o Double infusion rate to 0.5 mL/kg/min if BP remains low.
o Continue infusion for at least 10 minutes after cardiovascular
stability attained.
xxi
o Recommended upper limit: approximately 10 mL/kg
LoE:III
lipid emulsion over the first 30 minutes.
12.6.3 ANAESTHETIC-RELATED ACUTE HYPOTENSION
I95.81
Treat the cause of hypotension.
Ensure appropriate fluids are given to correct hypovolaemia.
The medicines given below all require significant dilution
administration.
before


Adrenergic and dopaminergic agents, e.g.:
Ephedrine IV, 3–5 mg as a single dose and then further boluses as
required to a maximum of 30 mg.
o Increases heart rate and contractility, and vasoconstrictor.
xxii
OR
LoE:III
Phenylephrine IV, 50–100 mcg as a single dose and then
2015
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
infuse at 60–180 mcg/minute.
xxiii
o Vasoconstrictor.
LoE:III
o High doses may cause significant reflex.
bradycardia: treat this by discontinuing the phenylephrine only.
12.6.4 ANAESTHESIA-RELATED ACUTE HYPERTENSION
I97.3
To obtund the hypertensive response to intubation i.e. pre-eclampsia:

Alfentanil, IV, 7.5 mcg/kg (with magnesium sulfate, IV 30 mg/kg)
LoE:III
During anaesthesia or post-operatively, establish the cause
(e.g. light anaesthesia or inadequate pain relief) and treat as appropriate.

Labetalol IV, 5–10mg IV over 2 minutes.
o Repeated at intervals of at least 5 minutes to maximum 200 mg.
o Duration of action 50 minutes.
xxiv
o Vasodilates and slows heart rate.
LoE:III
.
12.6.5 POSTOPERATIVE NAUSEA AND VOMITING (PONV)
12.6.5.1 PREVENTION OF PONV
R11.2
Patients identified preoperatively as medium or high risk for PONV should be
considered for prophylactic antiemetics.
Prophylactic antiemetics also required if postoperative vomiting is potentially
dangerous, e.g. after jaws wired, open eye surgery, oesophageal surgery.
High risk patients should receive anti-emetics from ≥ 1 class.
Adequate IV hydration associated with less PONV.
Risk factors for PONV
Female Gender
Non-Smoker
History of PONV and/or motion
sickness
Postoperative opioids
Sum
Points
0
1
2
3
4
2015
Points
1
1
1
1
0–4
Risk for PONV (%)
10
20
40
60
80
Risk category
Low
Low
Medium
High
High
12.10
CHAPTER 12
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Anti-emetic
Class
Prophylactic
Dose and timing
Notes
Dexamethasone
Corticosteroid
4-8 mg, IV, on
induction
Increases blood
glucose in diabetics.
Only used for
prophylaxis, not
established PONV.
Ondansetron
5-HT3 receptor
antagonist
4 mg, IV, over 2–
5 minutes at end
of surgery
Prolongs QTc
interval
Promethazine
Phenothiazine
6.25–12.5 mg, IV
(large bore
cannula) diluted
to 20 mL over 1020 minutes, or
deep IM, at end of
surgery.
Intra-arterial
injection causes
gangrene.
Extravasation or
subcutaneous
injection associated
with skin necrosis.
Anticholinergic side
effects and
sedation.
xxv
LoE:II
12.6.5.2 TREATMENT OF PONV
R11.2
Ensure adequate hydration and correct hypotension if present.
Give an emetic from a different class than the prophylactic agent given
(except dexamethasone, which is only used for prophylaxis).

Metoclopramide, IM/IV
o If < 60kg: 5mg IM or IV (over 2 minutes).
o If ≥ 60kg: 10mg IM or IV (over 2 minutes).
o Repeat 8 hourly if required.
Metoclopramide can cause extrapyramidal side effects.
Treat acute dystonic reactions with:

Anticholinergic agent, e.g.:

Biperiden, IM/IV, 2 mg.
o Repeat as necessary.
If an anticholinergic agent is not available:

Promethazine, deep IM, 25–50 mg.
o In the elderly 25 mg.
If an anticholinergic agent or promethazine is not available:

Diazepam, IV, 10 mg for symptom relief.
2015
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
12.6.6 ACID ASPIRATION PROPHYLAXIS
O74.0
The use of a non-particulate, non-effervescent antacid reduces the risk of
pneumonitis if gastric fluid is aspirated. Give to patients at risk of aspiration,
e.g. pregnant women before Caesarean section.

Sodium citrate, 0.3M, oral, 30 mL.
o Not more than 30 minutes pre-induction of anaesthesia.
xxvi
LoE:I
12.7 SPINAL (INTRATHECAL) ANAESTHESIA
Only preservative free medicines may be used.
Larger doses cause block to spread higher, with risks of respiratory
depression, hypotension and loss of consciousness.

Bupivacaine 0.5% (Spinal use)
o Give up to 3 mL according to desired level of block.
o Becomes hypobaric (light) within CSF so block may spread higher
than anticipated.

Bupivacaine 0.5% with dextrose (Spinal use)
o Give up to 3 mL according to desired level of block.
o Hyperbaric (heavy) so block spreads according to patient position.
Small amounts of fentanyl (10–25 mcg) may be added to increase duration
of analgesia.
Caesarean Section
Lower doses are required due to physiologic changes of pregnancy:

Bupivacaine, 1.8 mL (9 mg) plus dextrose.
AND

Fentanyl, 0.2 mL (10 mcg).
12.7.1 ANTICOAGULANTS AND SPINAL OR EPIDURAL
BLOCKS
Patients on anticoagulants are at risk of developing a spinal haematoma with
subsequent paralysis after a spinal or epidural block. These anticoagulants
should be stopped before the spinal or epidural is performed according to
the guidelines given below.
2015
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Timing of anticoagulants in patients receiving neuraxial anaesthesia:
Anticoagulant
Warfarin, oral
Unfractionated
SC
Heparin,
Unfractionated Heparin,
IV
Prophylactic LMWH, SC
Therapeutic LMWH, SC
Before Neuraxial Block
After Neuraxial block
Stop warfarin and check
INR normal
Restart after neuraxial
block
performed
and
epidural catheter removed.
Neuraxial techniques may be performed if total daily
dose is <10 000U. Check PTT if higher doses are
used.
Stop heparin >4 hours Wait >1 hour before next
and check PTT
bolus/infusion restarted
>12 hours after last dose >6 hours or at least 2
hours
after
epidural
catheter
removed,
whichever is later.
>24 hours after last dose >24 hours or at least 2
hours
after
epidural
catheter
removed,
whichever is later.
xxvii
LoE:II
Note. After neuraxial block or epidural catheter removal, patients should be
observed closely for new or progressive neurological symptoms. A spinal
haematoma can result in permanent paralysis unless decompressive
surgery is performed within 8 hours of paralysis onset.
Clopidogrel and platelet GPIIb/IIIa inhibitors have variable durations of
effects on clotting after stopping these medications. Specialist advice should
be sought before performing neuraxial blocks on patients receiving these
medications.
For patients on warfarin the use of bridging anticoagulation (giving heparin
after warfarin is stopped in preparation for surgery or invasive procedures)
remains unsettled. Practitioners should exercise careful judgment of
competing risks in individual patients. Heparin may increase the risk of
bleeding. Whatever practice is adopted the most important consideration is
to ensure that adequate anticoagulation with warfarin is re-instituted once
the risk of bleeding is past.
12.8 EPIDURAL ANAESTHESIA
Only preservative free medicines may be used.
Local anaesthetics are administered through a catheter inserted into the
epidural space at a spinal level appropriate for the surgery.
Aspiration and a test dose (2–3 mL) of local anaesthetic should be given to
confirm catheter not intravascular or intrathecal. Subsequent doses should
be fractionated (3–5 mL boluses).
2015
12.13
CHAPTER 12


ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Bupivacaine 0.5%.
o Onset ±10 minutes.
o Duration ±4 hours.
o Motor block is less with lower concentrations.
o Maximum dose 2 mg/kg.
Lidocaine 2% (preservative-free).
o Onset ±3-5 minutes.
o Duration ±1 hour.
12.9
xxviii
LoE:III
xxix
LoE:III
PERIPHERAL NERVE BLOCK OR WOUND
INFILTRATION
Only preservative free medicines may be used for nerve blocks.
Lignocaine has a faster onset of action than bupivacaine but a shorter
duration of action.

Lidocaine 1% or 2%.
o Higher concentrations cause more pain on injection.
o Maximum dose: 3 mg/kg.

Lidocaine 2% plus adrenaline.
o Not to be used in areas supplied by an end-artery e.g. finger, ear,
penis.
Maximum dose: 7 mg/kg.

Bupivacaine 0.5%
o Not be used in mucosal areas as risk of systemic toxicity.
o Maximum dose: 2 mg/kg.
xxx
LoE:III
12.10 TOPICAL ANAESTHESIA

Lidocaine jelly, topical, 2 g/100mL.
o For urethral catheterisation: female 5–7 mL, male 10–15 mL.
xxxi
LoE:III

Lidocaine topical spray, 4%.
o Maximum dose 160 mg.
o To assist with awake intubation or reduce haemodynamic response
to intubation.
xxxii
LoE:III
For venepuncture analgesia in adults or oncology patients
requiring repeated invasive procedures (e.g. lumbar punctures,
venepuncture):

Lidocaine/prilocaine, topical cream, 2.5/2.5%.
2015
12.14
CHAPTER 12
o
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Apply at least 1 hour before and cover with occlusive dressing.
xxxiii
LoE:III
12.11 SEDATION
Y47.9
Refer to chapter 23: Sedation.
12.12 PAIN, CHRONIC
R52.1
Pain is an unpleasant sensory and emotional experience associated with
actual or potential tissue damage.
ASSESSEMENT OF CHRONIC PAIN
The aetiology of the pain needs to be ascertained, and whether treatment of
the cause is possible.
Determine if the type of pain is nociceptive, neuropathic or both.
Depression and anxiety are commonly associated with chronic pain. Every
patient needs a psychological assessment.
If a patient is suffering from chronic pain due to a terminal illness, ascertain
the prognosis.
Response to current and previously used analgesic
comorbidities, and functional status should be established.
medication,
Use of a self-reporting pain scale helps to monitor treatment progress. See
Numeric Rating Scale in section 12.5.2: Postoperative pain in the recovery
room).
Pain at rest, on movement and during pain exacerbations should be
recorded. Patients must be monitored at regular intervals so treatment can
be adjusted appropriately.
GENERAL AND SUPPORTIVE MEASURES
Patients with chronic pain should be treated with a biopsychosocial
approach.
A multidisciplinary team approach is required and the assistance of
psychiatrists, physiotherapists, occupational therapists, social workers,
dieticians and psychologists should be sought according to the patient’s
needs.
The goals of pain management not only include pain reduction but also
improvement of function, sleep and well-being.
Family members play an important part in the patient’s treatment and should
be included where possible.
2015
12.15
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
MEDICINE TREATMENT
Chronic pain is rarely completely cured with medication. The aim of
pharmacological treatment is to reduce pain levels in order to maintain or
improve function.
Medications should preferably be given orally.
12.12.1 ANALGESIA FOR CHRONIC NON-CANCER PAIN
R52.1
For chronic pain of a constant nature, analgesics should be administered on
a regular basis.
MILD/MODERATE PAIN:
Paracetamol, ibuprofen and tramadol can be used alone or in combination
according to the severity of the pain.

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.

Ibuprofen, oral, 400 mg 8 hourly with meals.
o Can be used in combination with paracetamol or opioids.

Tramadol, oral, 50–100 mg, 6 hourly.
o Avoid in head injury and epilepsy.
o Improved effect when given with paracetamol.
Note:
» Tramadol blocks neuronal reuptake of noradrenaline and serotonin. If
used with other medicines that also block serotonin reuptake (e.g.
pethidine, fentanyl, antidepressants) the serotinergic syndrome can result
(altered mental status, neuromuscular hyperactivity, autonomic
hyperactivity).
» Avoid long-term use of NSAIDs as they are associated with an increased
risk of arterial thrombosis, renal impairment and gastrointestinal bleeding.
SEVERE PAIN:

Morphine syrup (Mist morphine), oral.
o Starting dose: 10–15 mg (maximum 0.2 mg/kg) 4 hourly.
o Elderly or frail patients: 2.5–5 mg oral (maximum 0.1 mg/kg) 4 hourly.
o Increase dose by 50% every 24 hours if pain control is inadequate.
o Reduce the dosing interval if there is regular breakthrough pain.
o Increase the dosing interval in patients with renal or liver impairment.
When stable on morphine syrup, the morphine syrup can be changed to an
equivalent dose of long- acting, slow release morphine:
2015
12.16
CHAPTER 12

ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Morphine, long-acting, oral, 12 hourly.
o Available in tablets of 10 mg and 30 mg.
o Duration of action 12 hours.
o Dose according to previous morphine syrup requirement: e.g. a
patient whose pain is controlled by 6 doses of morphine syrup 10
mg per 24 hours (i.e. 60 mg morphine per day) can be converted
to slow release morphine tablets, 30 mg 12 hourly, oral.
o Maximum dose for non-cancer pain is usually 60 mg 12 hourly.
Note:
» When morphine is used for chronic non-cancer pain, discuss potential
side-effects with the patient, the maximum dose of opioids that will be
prescribed and anticipated duration of treatment.
» Avoid in patients with history of alcohol or other drug addiction, where
possible.
12.12.2 ANALGESIA FOR CHRONIC CANCER PAIN
R52.1
The term “cancer pain” also includes pain due to terminal illness.
The same steps as given in section 12.12.1: Analgesia for chronic noncancer pain should be followed with the following exceptions:

»
»
»
Morphine:
There is no maximum dose of morphine that may be needed.
Concerns regarding addiction should not compromise adequate pain
control with opioids when used to treat terminal illnesses.
For terminally ill patients on slow release morphine, it is advisable to
still prescribe morphine syrup for breakthrough pain or for painful
procedures.
Note:
» Opioid–induced hyperalgesia, is defined as increasing pain sensitivity in
patients chronically exposed to opioids without any new causes for pain.
Increasing doses of morphine paradoxically result in increased pain,
often with features of neuropathic pain such as hyperalgesia or
allodynia.
» It can be managed by switching to methadone, in consultation with a
specialist familiar with the use of this agent.
xxxiv
LoE:III
12.12.3
TREATMENT OF ADVERSE
CHRONIC OPIOID USE
EFFECTS
OF
Y45.0
Constipation:
Patients on chronic opioids should routinely be prescribed a laxative.
2015
12.17
CHAPTER 12

ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Sennosides A and B, oral, 2 tablets at night.
o Contraindicated in patients with potentially obstructive lesions.
In patients with potentially obstructive lesions:

Lactulose, oral, 15 mL 12 hourly.
Nausea and vomiting:

Metoclopramide, oral/IM/slow IV, 10 mg 8 hourly (See section 12.7.5.2
treatment of PONV).
OR
Promethazine, oral, 10 mg 8 hourly.
LoE:III
OR

Ondansetron, oral, 8 mg 12 hourly.
12.12.4 ANALGESIA FOR CHRONIC NEUROPATHIC PAIN
G62.9
Neuropathic pain resulting from nerve injury or disease e.g. nerve root
compression, peripheral neuropathy due to diabetes or HIV.
In addition to the analgesics for chronic nociceptive pain (see section
12.13.1 Analgesia for chronic non-cancer pain), anti-neuropathic pain
medicines to stabilise affected sensory nerves can be used.
These medications must be used regularly, as they take 2–6 weeks to work.

Amitriptyline, oral, 10 mg, two hours before usual sleep time.
o Titrate up to 75 mg at night.
xxxv
LoE:II
If no response after 2-4 weeks, (or amitriptyline contraindicated):
ADD/REPLACE WITH

Carbamazepine, oral, 100–200 mg 12 hourly for 2 weeks.
o If response is inadequate, increase the dose every 2 weeks to a
maximum dose of 600 mg 12 hourly.
REFERRAL
For neuropathic pain unresponsive to these medicines, refer patient to a
experienced pain clinician.
12.12.5 ANALGESIA FOR ACUTE NON-SURGICAL PAIN
12.12.5.1 MEDICAL CONDITIONS ASSOCIATED WITH
SEVERE PAIN
R52.9
There are numerous medical conditions associated with severe acute pain
e.g. myocardial infarction, renal colic, sickle-cell crisis and intra-articular
2015
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
haemorrhage due to haemophilia.
The analgesic treatment for these conditions is as for patients with acute postoperative pain (see section 12.5.2: Postoperative pain in the recovery room).
Patients should be monitored for respiratory and cardiovascular depression
when IV opioids are administered.
Patients already on opioids for chronic pain, who experience an acutely
painful event, may be opioid tolerant and require higher IV opioid boluses in
order to control their pain.
12.12.5.2 ACUTE PAIN DUE TO GASTROINTESTINAL
COLIC
R10.84

Hyoscine butylbromide, IV/oral, 10 mg 8 hourly.
12.13 INTENSIVE CARE
12.13.1 NUTRITIONAL SUPPORT
E63.9
Establish a multidisciplinary nutrition support team to assess and address
the nutritional requirements of patients. This team should include a dietician.
Nutrition support should be considered in patients at risk, defined as those
who have a poor absorptive capacity and/or high nutrient losses and/or
increased nutritional needs from causes such as catabolism.
Oral feeding, if feasible, is preferred
Enteral tube feeding is the next best option
Total parenteral nutrition (TPN) is indicated in exceptional circumstances.
In selecting the treatment modality, the team should consider:
» The likely duration of nutrition support.
» Patient activity levels and the underlying clinical condition, e.g. catabolism.
» Gastrointestinal tolerance, potential metabolic instability and risks of refeeding.
Potential complications harms of nutritional support include:
» Re-feeding syndrome: Hypophosphataemia occurs when patients are
re-fed too quickly with high carbohydrate feeds. The syndrome usually
begins within 4 days of re-feeding. A multitude of life-threatening
complications involving multiple organs may occur, casuing: respiratory
failure, cardiac failure, cardiac dyshythmias, rhabdomyolysis, seizures,
coma, red cell and leukocyte dysfunction. The most effective way to
2015
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»
»
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
prevent re-feeding syndrome is that feeds should be started slowly with
aggressive supplementation of magnesium, phosphate and potassium.
Diarrhoea.
Lactose intolerance.
Regularly review the need for ongoing therapeutic nutritional support.
Vitamin and mineral supplementation should be considered on a case-bycase basis.
Enteral tube feeding
Enteral tube feeding should be used in patients who cannot swallow or who
are at risk of aspiration.
Patients should be fed via a nasogastric tube unless this is contra-indicated.
Patients with upper gastro-intestinal dysfunction (or an inaccessible upper
gastro-intestinal tract) should receive post-pyloric (duodenal or jejunal) feeding.
Percutaneous endoscopic gastrostomy feeding should be used in patients
likely to need long-term (≥4 weeks) enteral tube feeding.
Parenteral feeding
The team should consider parenteral nutrition in patients who are
malnourished or at risk of malnutrition and fit the following criteria:
» inadequate or unsafe oral and enteral tube nutritional intake, or
» a non-functional, inaccessible or perforated (leaking) gastrointestinal tract.
The current standard formulas in multi-chamber bags that have a long shelflife are considered to provide adequate nutritional support.
The addition of glutamine does not confer any clear clinical benefits
and is thus not recommended.
Parenteral nutrition can be withdrawn once adequate oral or enteral nutrition
is tolerated and nutritional status is stable. Withdrawal should be planned
and done in a stepwise way with a daily review of the patient’s progress.
References:
i
Lorazepam, oral: SAMF, 2014
ii
Sevoflurane: National Department of Health, Essential Drugs Programme. Medicine review: Sevoflurane, 5 March
2015. http://health.gov.za/
Sevoflurane: National Department of Health, Essential Drugs Programme. Cost analysis report for halothane
versus sevoflurane for induction of anaesthesia in adults at hospital level, 10 September 2015. http://health.gov.za/
iii
Suxamethonium: SAMF, 2014
iv
Vecuronium: SAMF, 2014
v
Suxamethonium: Perry JJ, Lee JS, Sillberg VA, Wells GA. Rocuronium versus succinylcholine for rapid
sequence induction intubation. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002788.
http://www.ncbi.nlm.nih.gov/pubmed/18425883
vi
Rocuronium: Perry JJ, Lee JS, Sillberg VA, Wells GA. Rocuronium versus succinylcholine for rapid sequence
induction intubation. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002788.
http://www.ncbi.nlm.nih.gov/pubmed/18425883
Rocuronium: Contract circular price: HP06-2014SVP. http://health.gov.za/
Rocuronium: National Department of Health, Essential Drugs Programme. Medicine review: Rocuronium for
muscle relaxation for rapid sequence induction, 31 March 2015. http://health.gov.za/
2015
12.20
CHAPTER 12
ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
vii
Neostigmine: SAMF, 2014
Atropine: SAMF, 2014
Glycopyrrolate: SAMF, 2014
x
Paracetamol, oral: The South African Society of Anaesthesiologists. South African Acute Pain Guidelines.
SAJAA 2009;15(6):1-120. http://www.sasaweb.com/content/images/SASA_Pain_Guidelines.pdf
Paracetamol: Bandolier. Oxford league table of analgesics in acute pain. Available at:
http://www.medicine.ox.ac.uk/bandolier/booth/painpag/acutrev/analgesics/leagtab.html
xi
Tramadol, oral: The South African Society of Anaesthesiologists. South African Acute Pain Guidelines. SAJAA
2009;15(6):1-120. http://www.sasaweb.com/content/images/SASA_Pain_Guidelines.pdf
xii
Ibuprofen, oral: The South African Society of Anaesthesiologists. South African Acute Pain Guidelines. SAJAA
2009;15(6):1-120. http://www.sasaweb.com/content/images/SASA_Pain_Guidelines.pdf
xiii
Fentanyl, IV: The South African Society of Anaesthesiologists. South African Acute Pain Guidelines. SAJAA
2009;15(6):1-120. http://www.sasaweb.com/content/images/SASA_Pain_Guidelines.pdf
Fentanyl, IV: Scholz J, Steinfath M, Schulz M. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil.
An update. Clin Pharmacokinet. 1996 Oct;31(4):275-92. http://www.ncbi.nlm.nih.gov/pubmed/8896944
xiv
Ketamine, IV: McNicol ED, Schumann R, Haroutounian S. A systematic review and meta-analysis of ketamine
for the prevention of persistent post-surgical pain. Acta Anaesthesiol Scand. 2014 Nov;58(10):1199-213.
http://www.ncbi.nlm.nih.gov/pubmed/25060512
xv
Tramadol, IV: Houmes RJ, Voets MA, Verkaaik A, Erdmann W, Lachmann B. Efficacy and safety of tramadol
versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Anesth
Analg. 1992 Apr;74(4):510-4. http://www.ncbi.nlm.nih.gov/pubmed/1554117
Tramadol, IV: National Department of Health, Essential Drugs Programme. Medicine review: Tramadolol, IV
July 2015. http://health.gov.za/
xvi
Ward prescriptions for postoperative analgesia according to anticipated pain severity: The South African
Society of Anaesthesiologists. South African Acute Pain Guidelines. SAJAA 2009;15(6):1-120.
http://www.sasaweb.com/content/images/SASA_Pain_Guidelines.pdf
xvii
Patient controlled analgesia: Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid
analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006 Oct
18;(4):CD003348. Review. Update in: Cochrane Database Syst Rev. 2015;6:CD003348..
http://www.ncbi.nlm.nih.gov/pubmed/17054167
xviii
Ringer lactate: SAMF, 2014.
Sodium chloride 0.9%: SAMF, 2014.
xix
Dantrolene: SAMF, 2014.
xx
Oxygen: Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and Pain Medicine.
American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic
toxicity: 2012 version. Reg Anesth Pain Med. 2012 Jan-Feb;37(1):16-8.
http://www.ncbi.nlm.nih.gov/pubmed/22189574
Diazepam, IV: Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and Pain
Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic
systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012 Jan-Feb;37(1):16-8.
http://www.ncbi.nlm.nih.gov/pubmed/22189574
Adrenaline (epinephrine): Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and
Pain Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local
anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012 Jan-Feb;37(1):16-8.
http://www.ncbi.nlm.nih.gov/pubmed/22189574
xxi
Lipid emulsion (20%), IV: Jamaty C, Bailey B, Larocque A, Notebaert E, Sanogo K, Chauny JM. Lipid
emulsions in the treatment of acute poisoning: a systematic review of human and animal studies. Clin Toxicol
(Phila). 2010 Jan;48(1):1-27. http://www.ncbi.nlm.nih.gov/pubmed/20095812
Lipid emulsion (20%), IV: Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and
Pain Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local
anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012 Jan-Feb;37(1):16-8.
http://www.ncbi.nlm.nih.gov/pubmed/22189574
Lipid emulsion (20%), IV: National Department of Health, Essential Drugs Programme. Cost analysis report for
intralipid 20% emulsion for local anesthetic systemic toxicity, 8 October 2015. http://health.gov.za/
xxii
Ephedrine, IV: SAMF, 2014.
xxiii
Phenylephrine, IV: SAMF, 2014.
xxiv
Labetalol, Scott DB. The use of labetalol in anaesthesia. Br J Clin Pharmacol. 1982 Jun;13(1 Suppl):133S135S. http://www.ncbi.nlm.nih.gov/pubmed/7093097
Labetalol, IV: Varon J, Marik PE. Perioperative hypertension management. Vascular Health and Risk
Management. 2008;4(3):615-627. http://www.ncbi.nlm.nih.gov/pubmed/18827911
xxv
Dexamethasone, IV: Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting.
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004125. http://www.ncbi.nlm.nih.gov/pubmed/16856030
Ondansetron, IV: Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane
Database Syst Rev. 2006 Jul 19;(3):CD004125. http://www.ncbi.nlm.nih.gov/pubmed/16856030
Promethazine, IV: Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane
Database Syst Rev. 2006 Jul 19;(3):CD004125. http://www.ncbi.nlm.nih.gov/pubmed/16856030
xxvi
Sodium citrate, solution: Paranjothy S, Griffiths JD, Broughton HK, Gyte GM, Brown HC, Thomas J.
viii
ix
2015
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ANAESTHESIOLOGY, PAIN, INTENSIVE CARE
Interventions at caesarean section for reducing the risk of aspiration pneumonitis. Cochrane Database Syst Rev.
2014 Feb 5;2:CD004943. http://www.ncbi.nlm.nih.gov/pubmed/24497372
Sodium citrate solution: National Department of Health, Essential Drugs Programme. Medicine review: Sodium
citrate solution to reduce the risk of aspiration pneumonitis in patients undergoing Caeserean section. September
2015. http://health.gov.za/
xxvii
Timing of anticoagulants: The BRIDGE Study Investigators .Bridging Anticoagulation: Is it Needed When
Warfarin Is Interrupted Around the Time of Surgery or a Procedure? Circulation 2012;125:e496-e498.
http://www.ncbi.nlm.nih.gov/pubmed/22451610
xxviii
Bupivicaine, 0.5%: SAMF, 2014.
xxix
Lidocaine 2% (preservative-free).SAMF, 2014.
xxx
Lidocaine 1% or 2%: SAMF, 2014.
Lidocaine 2% plus adrenaline: SAMF, 2014.
Bupivicaine 0.5%: SAMF, 2014.
xxxi
Lidocaine topical jelly: SAMF, 2014.
xxxii
Lidocaine topical spray: SAMF, 2014.
xxxiii
Lidocaine/prilocaine, topical cream, 2.5/2.5%.: Sharma SK, Gajraj NM, Sidawi JE, Lowe K. EMLA cream
effectively reduces the pain of spinal needle insertion. Regional anesthesia. 1996 Nov-Dec;21(6):561-4.
http://www.ncbi.nlm.nih.gov/pubmed/8956393
xxxiv
Methadone: Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG. Simultaneous targeting of
multiple opioid receptors: a strategy to improve side-effect profile. Br J Anaesth 2009; 103: 38–49.
http://www.ncbi.nlm.nih.gov/pubmed/19474215
Methadone: Holtman JR, Jr, Wala EP. Characterization of the antinociceptive and pronociceptive effects of
methadone in rats. Anesthesiology 2007; 106: 563–71. http://www.ncbi.nlm.nih.gov/pubmed/17325516
xxxv
Amitryptiline: Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults.
Cochrane Database Syst Rev. 2015 Jul 6;7:CD008242. http://www.ncbi.nlm.nih.gov/pubmed/26146793
Amitryptiline: Chetty S, Baalbergen E, Bhigjee AI, Kamerman P, Ouma J, Raath R, Raff M, Salduker S; South
African Expert Panel. Clinical practice guidelines for management of neuropathic pain: expert panel
recommendations for South Africa. S Afr Med J. 2012 Mar 8;102(5):312-25.
http://www.ncbi.nlm.nih.gov/pubmed/22554341
2015
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MUSCULOSKELETAL SYSTEM
13.1 ARTHRITIS, RHEUMATOID (RA)
M06.9
DESCRIPTION
A chronic, inflammatory, systemic condition with a fluctuating course. It may
affect many organs, but the joints are predominantly affected. Characteristic
joint manifestations are:
» Swelling or fluid, affecting at least 3 joint areas simultaneously.
» Pain.
» Limited movement with morning stiffness > 1 hour, which improves with
activity. This distinguishes osteoarthrosis from rheumatoid arthritis.
» Destruction and deformity of affected joints.
» The small joints of the fingers and hands, with the exception of the distal
interphalangeal joints, are usually involved, although any joint can be
involved.
» The involved joint distribution is typically symmetrical.
GENERAL MEASURES
Manage by co-ordinated multidisciplinary care.
The primary objective is to improve and maintain functional status.
Early use of non-drug measures, especially nursing, physiotherapy and
occupational therapy, is essential.
Acute flare-ups: rest affected joints and consider the use of day and/or night
splints.
Obtain a baseline complete blood count, serum creatinine, alanine
aminotransferase (ALT), and erythrocyte sedimentation rate (ESR) or Creactive protein (CRP) in all patients.
Obtain X-rays of the hands and wrists, as well as both forefeet to include the
metatarsophalangeal joints as a baseline for evaluating change in the joints
during treatment.
MEDICINE TREATMENT
All patients with suspected RA should be seen at an early stage by a
specialist. Evaluate all patients with suspected RA for disease-modifying
anti-rheumatic drug (DMARD):

Methotrexate (preferred initial therapy)

Chloroquine sulphate

Sulfasalazine
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MUSCULOSKELETAL SYSTEM
Patients on DMARDs must be monitored regularly for toxicity, as outlined
below:
Assess response to DMARD therapy by monitoring the number of swollen
and tender joints, restricted to 28 joints (shoulders, elbows, wrists, 5
metacarpophalangeal joints, 5 proximal interphalangeal joints and knees
bilaterally) together with ESR or CRP.
If there is poor response to one DMARD, add another DMARD.

Methotrexate, oral, 7.5 mg once per week. Specialist consultation.
o Increase dose gradually to a maximum of 25 mg per week.
o Monitor: ALT and FBC before and 12 weekly during treatment.
AND

Folic acid, oral, 5 mg per week at least 24 hours after the methotrexate
dose.
i
LoE:II
AND/OR

Chloroquine sulphate, oral, 150 mg (as base) daily for 5 days of each
week for 2–3 months.
o Do ophthalmic examination at baseline within the first year of
treatment and annually thereafter, to monitor for ocular damage.
AND/OR

Sulfasalazine, oral, 500 mg 12 hourly.
o Gradually increase over one month from 500 mg to 1 g 12 hourly.
o FBC and ALT monthly for first 3 months then every 3–6 months.
Oral corticosteroids
Systemic corticosteroids are effective at relieving symptoms in RA and have
been shown to modify the course of the disease, but long term use is
discouraged because this is associated with considerable toxicity, notably
osteoporosis, which is very common in patients with RA.
Indications:
» As bridging therapy while waiting for DMARDs to take effect.
» Acute disease flares.
» Severe extra-articular manifestations, e.g. scleritis.

Prednisone, oral, 40 mg daily for 2 weeks.
o Thereafter gradually reduce the dose to  7.5 mg daily. (Refer to
page xxvii for an example of a dose reduction regimen).
o Discontinue at 3–6 months.
ii
o The continued need for systemic steroids should
LoE:II
always prompt review of treatment.
Patients requiring corticosteroids for longer than 3 months should be
educated to take in enough calcium in their diet.
2015
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MUSCULOSKELETAL SYSTEM
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
NSAIDs
NSAIDs are used for symptomatic relief in patients with active inflammation
and pain. They have no long-term disease modifying effects.
NSAID dose should be reduced and then stopped once the DMARDs have
taken effect.
Reduce NSAID doses in the elderly.
NSAIDs are relatively contra-indicated in patients with significantly impaired
renal function, i.e. eGFR < 60 mL/minute.
Concomitant use of more than one oral NSAID has no additional clinical
benefit and only increases toxicity.
Chronic use of all NSAIDs is associated with increased risks of
gastrointestinal bleeding, renal failure, and cardiovascular events (stroke
and myocardial infarction).


NSAID, e.g.:
Ibuprofen, oral, 400 mg 8 hourly with meals.
iii
LoE:I
An extra night-time dose of a NSAID may be added in some patients with
severe nocturnal pain/morning stiffness.
Note: When an additional night-time dose is added to the patient’s regimen,
the risk of NSAID toxicity increases. A reduction in the daytime dose of
NSAIDs is recommended as the night-time dose will often exceed the
recommended total daily NSAID dose.
If a reduction in daytime dose causes increased pain, then the use of the
night-time dose must be for the shortest period possible.
In high-risk patients: > 65 years of age; history of peptic ulcer disease; on
concomitant warfarin, aspirin, or corticosteroids:
iv
ADD
LoE:III

Lansoprazole, oral, 30 mg daily whilst on an NSAID.
Adjunct for pain control:

Amitriptyline, oral, 10–25 mg at night.
o Titrate dose according to response.
o Initial dose in the elderly: 10 mg at night.
o Maximum dose: 75 mg at night.
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o
MUSCULOSKELETAL SYSTEM
Use with caution in patients with angle closure glaucoma, prostatic
hypertrophy and the elderly.
Intra-articular corticosteroids
Consider only in cases where a few joints are very actively inflamed.
To be prescribed and administered by a specialist.
Not more than 2–3 injections per year per joint are recommended.

Intra-articular corticosteroid, e.g.:

Methylprednisolone acetate, 20–80 mg depending on joint size.
REFERRAL
»
»
»
»
»
At initial diagnosis.
Disease activity cannot be controlled with the measures as mentioned.
Compression neuropathy.
For joint replacement.
Allergy to sulfasalazine.
Urgent
»
»
»
»
»
Rupture of tendons.
Scleritis.
Unstable upper cervical spine.
Vasculitis.
Cricoarytenoid joint involvement with hoarseness and inspiratory stridor.
13.2 ARTHRITIS, SEPTIC AND OSTEOMYELITIS, ACUTE
M00.9/M86.1
DESCRIPTION
An acute infective condition involving one or more joints.
The joint is hot, swollen, very painful on movement, and with restricted
movements.
Signs of systemic infection, including fever, are usually present. The infection
is usually blood borne, but may follow trauma to the joint. The course may be
acute or protracted. The commonest causative organism is Staphylococcus
aureus, but a large number of other organisms may be involved, including and
N. gonorrhoeae.
Note: Haemophiliacs with bleeding into joints may present with an acute
arthritis mimicking septic arthritis.
GENERAL MEASURES
Baseline X-ray.
Rest and immobilisation.
Septic arthritis:
Drainage is important. Discuss with an appropriate specialist.
2015
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MUSCULOSKELETAL SYSTEM
MEDICINE TREATMENT
Empiric antibiotic therapy
Therapy is directed against S. aureus unless there is evidence of urethritis or
PID, in which case gonococcal infection should be covered.
It is crucial to obtain cultures of blood, joint or other fluids before administering
antibiotics.

Cloxacillin, IV, 2 g 6 hourly for 4 weeks.
After 2 weeks of IV therapy, a change to oral therapy may be considered in
patients with a good clinical response:

Flucloxacillin, oral, 1 g 6 hourly to complete the 4 weeks’ treatment.
Severe penicillin allergy:
 Clindamycin, IV, 600 mg 8 hourly.
After 2 weeks of IV therapy, a change to oral therapy may be considered in
patients with a good clinical response:

Clindamycin, oral, 450 mg 8 hourly to complete the 4 weeks’ treatment.
v
LoE:III
For gonococcal arthritis

Ceftriaxone, IV, 1 g daily for 1 week.
Severe penicillin allergy:
Refer.
Analgesia

NSAID until pain subsides e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
vi
LoE:I
AND/OR

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
REFERRAL
»
»
»
»
Acute osteomyelitis/ septic arthritis for early drainage by specialist
surgeon.
If pyrexia persists in spite of adequate antibiotic therapy, a subperiosteal abscess must be sought and drained by a specialist surgeon.
Chronic osteomyelitis.
Pathological fractures.
13.3 OSTEO-ARTHRITIS
M19.9
DESCRIPTION
A disorder typically affecting weight-bearing joints and the hand (distal and
2015
13.5
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MUSCULOSKELETAL SYSTEM
proximal interphalangeals, and first metacarpo-phalangeal joints).
Signs and symptoms include:
» Pain on effort, relieved by rest.
» Morning stiffness, lasting < 30 minutes.
» Limited movement.
» Joint swelling (effusions and/or osteophytes).
GENERAL MEASURES
Weight reduction.
Exercise: postural and non-weight bearing. Quadriceps strengthening for
knee involvement.
Support and alleviate weight bearing of affected joints, i.e. walking stick.
Physiotherapy and/or occupational therapy.
MEDICINE TREATMENT
When only pain relief is required:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
If ineffective:
ADD

NSAIDs e.g.:
vii
LoE:I

Ibuprofen, oral, 400 mg 8 hourly with meals.
As many of these patients, particularly the elderly have concomitant medical
conditions such as cardiovascular, gastrointestinal disease or renal function
impairment, NSAIDs must be used with caution.
Patients on aspirin for cardiovascular risk reduction should take this agent 30
st
minutes before the 1 dose of ibuprofen in the morning, as taking aspirin and
viii
ibuprofen at the same time may reduce aspirin’s efficacy.
LoE:III
In high-risk patients: > 65 years of age; history of peptic ulcer disease; or on
concomitant warfarin, aspirin or corticosteroids:
ix
ADD
LoE:III

Lansoprazole, oral, 30 mg daily.
Adjunct for pain control:

Amitriptyline, oral, 10–25 mg at night.
o Titrate dose according to response.
o Initial dose in the elderly: 10 mg at night.
Intra-articular corticosteroids
Consider in cases where a joint is actively inflamed.
To be prescribed and administered by a specialist only.
Not more than 2–3 injections per year per joint are recommended.

Intra-articular corticosteroid, e.g.:
2015
13.6
CHAPTER 13

MUSCULOSKELETAL SYSTEM
Methylprednisolone acetate, 20–80 mg depending on joint size.
REFERRAL
»
»
»
For consideration for joint replacement.
Intractable pain.
Neurogenic compression.
13.4 GOUT
M10.9
DESCRIPTION
A metabolic disease in which uric acid crystal deposition occurs in joints and
other tissues.
Acute gout:
Joint involvement is characterized by recurrent attacks of acute arthritis,
which usually affects one joint, and is accompanied by extreme pain and
tenderness, swelling, redness, and local heat.
» The inflammation may extend beyond the joint.
» In many patients the first metatarso-phalangeal joint is initially involved.
» The instep, ankle, heel, and knee are also commonly involved.
» Bursae (such as the olecranon) may be involved.
Chronic gout:
Gout with one or more of the following:
» uric acid deposits in and around joints, bursae and cartilages of the
extremities (tophi)
st
» initial involvement of the 1 metatarsal phalangeal joint in most patients
» involvement of the instep, ankle, heel and knee
» involvement of bursae (such as the olecranon)
» significant periarticular inflammation
» serum uric acid over 0.5 mmol/L
» bone destruction
» prolongation of attacks, often with reduction in pain severity
» incomplete resolution between attacks
GENERAL MEASURES
Acute attack
Rest and immobilisation.
Chronic gout
Lifestyle modification, including high fluid intake.
Avoid alcohol intake.
If possible, avoid diuretics, or use the lowest dose possible.
2015
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MUSCULOSKELETAL SYSTEM
MEDICINE TREATMENT
Acute gout
Initiate treatment as early as possible in an acute attack:

NSAIDs e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals for the duration of the
x
attack.
LoE:I
If NSAIDS are contraindicated, e.g. peptic ulceration, warfarin therapy and
renal dysfunction:

Prednisone, oral, 40 mg daily for 5 days.
Chronic gout
If possible, avoid known precipitants and medicines that increase uric acid,
including:
» low dose aspirin,
» ethambutol,
» pyrazinamide, and
» thiazide and loop diuretics.
Investigate for and treat secondary causes (e.g. haematological
malignancies) where possible.
Assess renal function and blood urate level. The serum uric acid level may
be normal during acute attacks.
Uric acid lowering therapy
Urate lowering therapy is required in the following:
» >2 acute attacks per year
» urate renal stones
» chronic tophaceous gout
» urate nephropathy
When the acute attack has settled, i.e. usually after 2 weeks:

Allopurinol, oral, 100 mg daily.
o Increase monthly by 100 mg according to urate blood levels and
eGFR.
o Titrate dose to reduce serum urate to < 0.35 mmol/L.
o Most patients will be controlled with a dose of 300 mg daily.
o Elderly and patients with renal impairment (eGFR between 30–60
mL/minute): start with 50 mg daily.
Allopurinol is contra-indicated in patients with eGFR < 30 mL/minute.
To prevent breakthrough gout attacks:

Colchicine, oral, 0.5 mg 12 hourly for 3 months.
OR

NSAIDs e.g.:

Ibuprofen, oral, 400 mg 12 hourly with meals for 3 months.
LoE:III
In high-risk patients: i.e. patients > 65 years of age, or with a history of peptic
ulcer disease, or on concomitant warfarin, aspirin or corticosteroids:
2015
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MUSCULOSKELETAL SYSTEM
ADD

Lansoprazole, oral, 30 mg daily.
xi
LoE:III
Do not stop uric acid lowering drugs during an acute attack.
REFERRAL
»
»
»
»
No response to treatment despite adequate adherence.
Suspected secondary gout.
Non-resolving tophaceous gout.
Patients with eGFR < 30 mL/minute.
13.5 SERONEGATIVE SPONDYLARTHRITIS
M45–49
DESCRIPTION
A group of diseases in which the rheumatoid factor is usually negative and
the spine is often involved. These disorders have certain similar clinical
features and occur predominantly in individuals with HLA-B27 antigen. The
rheumatological manifestations in these disorders are variable, typically
including asymmetrical lower-limb arthritis, sacro-iliitis, spinal inflammation
(spondylitis),
and
enthesitis
(e.g.,
Achilles
tendonitis).
The
spondyloarthritides include ankylosing spondylitis, reactive arthritis, psoriatic
arthropathy, and the arthritides associated with inflammatory bowel disease.
Extra-articular manifestations may occur, especially uveitis, which occurs in
about one third of patients.
GENERAL MEASURES
Physiotherapy to prevent back deformity.
MEDICINE TREATMENT
Initiate treatment with NSAIDs.

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
REFERRAL
»
»
»
Uveitis, to an ophthalmologist.
Refractory severe arthritis, to a rheumatologist.
Deformity at diagnosis, to a rheumatologist.
2015
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MUSCULOSKELETAL SYSTEM
13.5.1 ARTHRITIS, REACTIVE
M02.3
DESCRIPTION
A spondylarthritis often preceded by enteric or urogenital infections 1–4
weeks before the arthritis and occurring predominantly in individuals with
HLA-B27 antigen.
It is a clinical diagnosis with no laboratory test or radiographic findings.
It occurs more commonly in HIV infection.
It is usually self-limiting. However, joint symptoms may persist.
MEDICINE TREATMENT
Start with a high dose and titrate downwards if not needed or if not tolerated:

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg 8 hourly with meals.
xii
LoE:I
If urethritis is present, treatment may prevent further
episodes of arthritis:

Ceftriaxone, IM, 250 mg as a single dose.
o For ceftriaxone IM injection: Dissolve ceftriaxone 250 mg in 0.9 mL
lidocaine 1% without epinephrine (adrenaline).
AND

Azithromycin, oral, 1 g, as a single dose.
xiii
LoE:III
13.6 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
L93
These patients need to be managed by a specialist.
GENERAL MEASURES
Education regarding the disease and complications.
Avoid cigarette smoking as it is a trigger for lupus.
Avoid sunlight exposure. Sun protective barrier creams are often indicated.
Regularly monitor urine for blood and protein.
Advice regarding family planning as pregnancy may cause a lupus flare.
MEDICINE TREATMENT
Mild disease
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND/OR
2015
13.10
CHAPTER 13


MUSCULOSKELETAL SYSTEM
NSAIDs, e.g.:
Ibuprofen, oral, 400 mg 8 hourly with meals.
xiv
LoE:II
To suppress disease activity

Chloroquine sulphate, oral, 150 mg (as base) daily for 5 days of each
week.
o Do ophthalmic examination at baseline within the first year of
treatment and annually, to monitor for ocular damage.
xv
LoE:I
Corticosteroids
Initiate therapy in patients with life threatening manifestations and organ
involvement.

Prednisone, oral, 2 mg/kg daily, initial dose.
o Taper to the lowest maintenance dose after a response has been
obtained. Refer to page xxvii for an example of a dose reduction
regimen.
o Usual maintenance dose: 10 mg daily.
Patients requiring corticosteroids for > 3 months should be educated to take
in enough calcium in their diet.
Additional immunosuppressive therapy
Is often required for life-threatening disease. particularly kidney and CNS
involvement. These medicines should be initiated by a specialist.

Azathioprine, oral, 1 mg/kg daily, titrated to a maximum of 3 mg/kg daily.
OR
LoE:III
Cyclophosphamide, oral, 100 mg daily, titrated to a
maximum of 200 mg daily (or 1–3 mg/kg daily).
LoE:III
Raynaud’s phenomenon

Amlodipine, oral, 5 mg daily.
xvi
Antiphospholipid antibody syndrome

Aspirin, oral, 150 mg daily.
LoE:II
Patients with previous thrombo-embolic episodes should receive lifelong
warfarin (target INR 3 to 4).
LoE:III
Hormonal therapy in women
The use of oral contraceptives is controversial.
Until there is clarity it is advisable to use either progesterone-only, or low
dose oestrogens, or non-hormonal methods.
REFERRAL
»
»
»
»
»
All patients to a specialist for initial assessment.
Lupus flare.
Nephritis for renal biopsy.
Persistent haematological derangements i.e. thrombocytopaenia.
Neurological manifestations of lupus.
2015
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CHAPTER 13
MUSCULOSKELETAL SYSTEM
References:
i
Folic acid: Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, Bombardier C, Wells
GA, Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for
rheumatoid arthritis. Cochrane Database Syst Rev. 2013 May 31;5:CD000951.
http://www.ncbi.nlm.nih.gov/pubmed/24737913
ii
Prednisone (3-6 months): Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van
Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde
DM, Boonen A, van der Linden S. Randomised comparison of combined step-down prednisolone, methotrexate
and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309-18.
Erratum in: Lancet 1998 Jan 17;351(9097):220. http://www.ncbi.nlm.nih.gov/pubmed/9251634
Prednisone (3-6 months): Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens
PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF,
van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment
strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis
Rheum. 2005 Nov;52(11):3381-90. http://www.ncbi.nlm.nih.gov/pubmed/16258899
Prednisone (3-6 months): Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E,
McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A,
Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T.
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis
Rheumatol. 2016 Jan;68(1):1-26. http://www.ncbi.nlm.nih.gov/pubmed/26545940
iii
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen dose: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen dose: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and
ibuprofen tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
iv
Lansoprazole: Contract circular HP09-2014SD. http://www.health.gov.za
Lansoprazole (high risk patients on chronic NSAID therapy): McQuaid KR , Laine L . Systemic review and metaanalysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med
2006;119:624–38. http://www.ncbi.nlm.nih.gov/pubmed/16887404
Lansoprazole (high risk patients on chronic NSAID therapy): Serrano P, Lanas A, Arroyo MT, Ferreira IJ. Risk of
upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.
Aliment Pharmacol Ther. 2002 Nov;16(11):1945-53. http://www.ncbi.nlm.nih.gov/pubmed/12390104
Lansoprazole(high risk patients on chronic NSAID therapy): Lanza FL, Chan FK, Quigley EM; Practice
Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related
ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38. http://www.ncbi.nlm.nih.gov/pubmed/19240698
v
Clindamycin, oral dose: Bouazza N, Pestre V, Jullien V, Curis E, Urien S, Salmon D, Tréluyer JM. Population
pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis. Br J Clin
Pharmacol. 2012 Dec;74(6):971-7. http://www.ncbi.nlm.nih.gov/pubmed/22486719
Clindamycin, oral dose: Wasserman et al. South African antibiotic stewardship programme (SAASP): A pocket
guide to antibiotic prescribing for adults in South Africa, 2014.
http://www.fidssa.co.za/images/SAASP_Antibiotic_Gudidelines_2015.pdf
vi
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen dose: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen dose: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and
ibuprofen tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
vii
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen dose: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen dose: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and
ibuprofen tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
viii
Ibuprofen-aspirin interaction: Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N. The antiplatelet
effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy
2015
13.12
CHAPTER 13
MUSCULOSKELETAL SYSTEM
volunteers. Am J Cardiol. 2008 Apr 1;101(7). http://www.ncbi.nlm.nih.gov/pubmed/18359332
Ibuprofen-aspirin interaction: Meek IL, Vonkeman HE, Kasemier J, Movig KL, van de Laar MA. Interference of
NSAIDs with the thrombocyte inhibitory effect of aspirin: a placebo-controlled, ex vivo, serial placebo-controlled
serial crossover study. Eur J Clin Pharmacol. 2013 Mar;69(3):365-71.
http://www.ncbi.nlm.nih.gov/pubmed/22890587
ix
Lansoprazole: Contract circular HP09-2014SD. http://www.health.gov.za
Lansoprazole (high risk patients on chronic NSAID therapy): McQuaid KR , Laine L . Systemic review and metaanalysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med
2006;119:624–38. http://www.ncbi.nlm.nih.gov/pubmed/16887404
Lansoprazole (high risk patients on chronic NSAID therapy): Serrano P, Lanas A, Arroyo MT, Ferreira IJ. Risk of
upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.
Aliment Pharmacol Ther. 2002 Nov;16(11):1945-53. http://www.ncbi.nlm.nih.gov/pubmed/12390104
Lansoprazole(high risk patients on chronic NSAID therapy): Lanza FL, Chan FK, Quigley EM; Practice
Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related
ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38. http://www.ncbi.nlm.nih.gov/pubmed/19240698
x
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and ibuprofen
tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
xi
Lansoprazole: Contract circular HP09-2014SD. http://www.health.gov.za
Lansoprazole (high risk patients on chronic NSAID therapy): McQuaid KR , Laine L . Systemic review and metaanalysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med
2006;119:624–38. http://www.ncbi.nlm.nih.gov/pubmed/16887404
Lansoprazole (high risk patients on chronic NSAID therapy): Serrano P, Lanas A, Arroyo MT, Ferreira IJ. Risk of
upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.
Aliment Pharmacol Ther. 2002 Nov;16(11):1945-53. http://www.ncbi.nlm.nih.gov/pubmed/12390104
Lansoprazole(high risk patients on chronic NSAID therapy): Lanza FL, Chan FK, Quigley EM; Practice
Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related
ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38. http://www.ncbi.nlm.nih.gov/pubmed/19240698
xii
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and ibuprofen
tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
xiii
Ceftriaxone, IM: National Department of Health STI Guidelines, 2014 and PHC STGs and EML, 2014.
http://www.health.gov.za
Lidocaine 1% with epinephrine (adrenaline): National Department of Health STI Guidelines, 2014 and PHC STGs
and EML, 2014. http://www.health.gov.za
Azithromycin: National Department of Health STI Guidelines, 2014 and PHC STGs and EML, 2014.
http://www.health.gov.za
xiv
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Adverse effects of NSAIDs
medicine review. http://www.health.gov.za
NSAIDs as a therapeutic class: Affordable Medicines, EDP-Adult Hospital level. Naproxen, meloxicam and
piroxicam in arthritis medicine review. http://www.health.gov.za
Ibuprofen: Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N. The correlation between blood
levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther. 1986 Jul;40(1):1-7.
http://www.ncbi.nlm.nih.gov/pubmed/3522030
Ibuprofen: Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and ibuprofen
tablets in postoperative dental pain. Br J Oral Maxillofac Surg. 1996 Feb;34(1):110-4.
http://www.ncbi.nlm.nih.gov/pubmed/8645662
xv
Chloroquine: Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects
of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010 Jan;69(1):20-8.
http://www.ncbi.nlm.nih.gov/pubmed/19103632
xvi
Amlodipine: Ennis H, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's
phenomenon. Cochrane Database Syst Rev. 2014 Jan 30;1:CD002069.
http://www.ncbi.nlm.nih.gov/pubmed/24482037
2015
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NEUROLOGICAL DISORDERS
14.1 CEREBROVASCULAR DISEASE
14.1.1 STROKE
I64
GENERAL MEASURES
Optimise hydration and nutrition; insert nasogastric tube if patient cannot
swallow. Take precautions to ensure an open airway if patient is
unconscious.
Physiotherapy and good nursing care. Consider rehabilitation for suitable
patients, refer if necessary.
Do an ECG to rule out an acute coronary event or atrial fibrillation as
precipitants.
Do serology to exclude meningovascular syphilis.
Check lipid profile if there are clinical features to suggest dyslipidaemia.
Although the finding of a carotid bruit in a symptomatic patient should lead to
further investigation, its absence does not exclude significant carotid stenosis.
Ischaemic stroke in young adults (< 45 years of age) may be due to
atherosclerosis, but also consider:
1. Embolic: e.g. rheumatic heart disease, atrial fibrillation, cardiomyopathy,
previous myocardial infarction, and, very rarely, patent foramen ovale:
history, careful clinical cardiac examination, ECG/CXR, and
echocardiography
2. Vessel wall disease: e.g. syphilis HIV infection, collagen-vascular
diseases, or related to acute or chronic meningitis, and other rarer
disorders such as sarcoidosis and Wegener’s granulomatosis, and
extracranial arterial dissection. Investigate as dictated by clinical
presentation, but at least syphilis and HIV serology, urine dipstix
(haematuria and/or proteinuria), and ANF/RF. ANCA, and cerebral
angiography or carotid Doppler may be indicated. Although the finding
of a carotid bruit in a symptomatic patient should lead to further
investigation, its absence does not exclude significant carotid stenosis.
3. Hypercoagulable states: e.g. antiphospholipid antibody syndrome,
thrombotic thrombocytopenic purpura. Useful screening investigations
are FBC and, in women, PTT/Anti-phospholipid Ab. Testing for
thrombophilias and their management should only be done in
consultation with an expert.
MEDICINE TREATMENT
Measures for secondary prevention may not be appropriate for patients with
severe disability.
2015
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CHAPTER 14
All patients not on anticoagulation:

Aspirin, oral, 150 mg daily with meals.
NEUROLOGICAL DISORDERS
i
LoE: I
Patients with a thrombotic stroke for secondary prevention, irrespective of
the LDL level:

HMGCoA reductase inhibitors e.g.:

Simvastatin, oral, 10 mg at night.
ii
LoE:I
For DVT prophylaxis, low dose subcutaneous heparin:

Unfractionated heparin, SC, 5 000 units 12 hourly.
OR
Enoxaparin, SC, 40 mg daily.
See section 2.13: Venous Thrombo-Embolism.
In patients with cardioembolic strokes (e.g. atrial fibrillation) start
anticoagulation with warfarin 7 days after an index event provided there is no
haemorrhage on CT scan.
iii
LoE:III
Bridging anticoagulation with heparin, or earlier initiation of
warfarin, is not recommended because, although it reduces ischaemic stroke
recurrence, it causes an equivalent increase in symptomatic intracranial
haemorrhage.
LoE:III
Treat secondary pulmonary and urinary tract infections appropriately.
Blood pressure management
A transient increase in BP is common after an acute stroke. Do not actively
lower a BP of less than 220/120 mmHg in the first few days after stroke as this
may be associated with an increased risk of death.
In patients presenting with stroke and BP > 220/120 mmHg lower BP to about
180/110 in the first 24 hours.
If BP > 220/120 mm Hg:

Long-acting calcium channel blocker, e.g.:

Amlodipine, oral, 5 mg daily.
OR
If adequate fluid intake can be ensured:

Thiazide diuretic, e.g.:

Hydrochlorothiazide, oral, 25–50 mg daily.
iv
LoE:I
Good long term BP control is important for patients whose BP remains
elevated after the first few days
REFERRAL
To a facility with a CT scan.
» Patients with atypical clinical presentation.
» Selected patients with suspected ischaemic stroke who may benefit
2015
14.2
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»
»
NEUROLOGICAL DISORDERS
from thrombolysis with tissue plasminogen activator if initiated within 3
hours of onset of symptoms.
Patients with suspected posterior cerebral fossa haemorrhage who may
require surgical decompression.
If there is a history suggestive of subarachnoid haemorrhage or if there
is neck stiffness
14.1.2 TRANSIENT ISCHAEMIC ATTACK (TIA)
G45.9
DESCRIPTION
A transient ischaemic attack is an episode of the brain, spinal cord, or retinal
ischaemia causing focal neurological dysfunction usually for less than one
hour. Risk of subsequent stroke is highest in the week after a TIA. Consider
hypoglycemia, epilepsy and migraine as alternative causes for the
symptoms.
2
The ABCD scoring system:
Feature
Points
≥ 60 years of age
1
BP ≥ 140/90 mmHg
1
Clinical features:
speech disturbance without weakness OR
1
unilateral weakness
2
Diabetes
1
Duration:
10 to 59 minutes OR
1
≥ 1 hour
2
2
ABCD score of ≥4 is regarded as high risk and warrants urgent investigation
and management as the risk of stroke within the next week is ≥4%.
MEDICINE TREATMENT
Identified cardioembolic disease:

Warfarin, oral, 5 mg daily.
o INR should be done after 48 hours, then every 1 to 2 days until
within the therapeutic range of 2 to 3 (refer to Initiation dosing
tables in the Appendix II).
o Adjust dose to keep INR within therapeutic range (refer to
Maintenance dosing tables in the Appendix II).
v
LoE:III
Other patients:

Aspirin, oral, 150 mg daily.
vi
AND
LoE:I

HMGCoA reductase inhibitors e.g.:

Simvastatin, oral, 10 mg at night.
Manage hypertension.
2015
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NEUROLOGICAL DISORDERS
14.1.3 ACUTE SPINAL CORD INJURY
T09.3
There is no convincing evidence that high dose corticosteroids are beneficial
vii
in the management of traumatic cord injuries.
LoE:I
14.1.4 SUBARACHNOID HAEMORRHAGE
I60
DESCRIPTION
Bleeding into the subarachnoid space, most commonly due to the rupture of a
vascular aneurysm. Patients frequently present with an acute onset of severe
headache and may have additional neurological symptoms and signs.
Diagnosis is confirmed preferably by neurological imaging and, when this is
not available, urgently by lumbar puncture, demonstrating xanthochromia.
GENERAL MEASURES
Maintain normal hydration and electrolyte status.
Control blood pressure.
MEDICINE TREATMENT
Analgesia if level of consciousness is not impaired:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
If no response:
 Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Avoid NSAIDs.
In patients with grades 1 to 3 impairment of consciousness level while waiting for
transfer to neurosurgical facility and in consultation with neurosurgeon:

Nimodipine, oral, 60 mg 4 hourly for 21 days.
REFERRAL
All patients with minimal impairment of consciousness level for angiography
and appropriate neurosurgical management. Patients initially deemed
unsuitable for further investigation, may be referred at a later stage, should
their condition improve.
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NEUROLOGICAL DISORDERS
14.2 DEMENTIA
F02*
DESCRIPTION
Progressive loss of cognitive function, usually of insidious onset. Initial
presentation may be with mild personality or memory changes, before more
pronounced defects become evident.
Investigate patients for treatable (reversible) systemic, neurological and
psychiatric illnesses.
Common reversible causes of dementia include:
» Metabolic
- Hypothyroidism
- Vitamin B12 deficiency
- Pellagra
- Thiamine deficiency (Wernickes syndrome)
» Medications and drugs
- Alcohol abuse
- Many medications with CNS side effects
» Infections
- Syphilis
- HIV dementia
» Surgical
- Chronic subdural haematoma
- Normal pressure hydrocephalus
» Severe depression
Conditions which may worsen already existing dementia include:
» Electrolyte disturbances and dehydration.
» Infections, usually originating from the respiratory or urinary tract.
» Medication toxicity.
GENERAL MEASURES
Appropriate care and support, according to the level of impairment.
Ambulatory care is preferred to hospitalisation, if feasible.
Family counselling and support.
MEDICINE TREATMENT
Management is mainly symptomatic.
To control restless patients:

Haloperidol, oral, 0.5–1 mg 8 hourly with a higher dose at night, if
required.
For pellagra:

Nicotinamide, oral, 100 mg 8 hourly.
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NEUROLOGICAL DISORDERS
Wernickes syndrome

Thiamine, IV, 500 mg 12 hourly for 3 days, followed by 500 mg daily for
3–5 days.
o Follow with oral thiamine 100 mg 8 hourly.
Prophylaxis in patients at risk (alcoholism, malnutrition):

Thiamine, IM/oral, 100 mg 8 hourly for 14 days.
Treat other commonly associated nutritional deficiencies:

Vitamin B complex, oral, 2 tablets 8 hourly.
viii
LoE:III
LoE:III
14.3 EPILEPSY
G40
GENERAL MEASURES
Take an adequate history to define the type of epilepsy.
Although rare, juvenile myoclonic epilepsy and absence seizures should be
specifically considered and identified, as some standard medications may be
less efficacious in these conditions or may even worsen seizure frequency or
severity.
All patients with new onset epilepsy should have a CT scan and other
investigations as clinically indicated.
A single unprovoked seizure is usually not an indication for treatment,
although 40% of patients may have a subsequent seizure within 2 years.
Anticonvulsants should be commenced after a single unprovoked seizure in
patients at high risk of subsequent seizures (e.g. abnormal neurological
examination, strong family history, abnormal brain imaging)
Record dates and, if possible, times of seizures in a seizure diary. Present
seizure diary at each consultation for assessment of therapy.
Disease identification bracelet, necklace or card.
Counselling and advice on:
» the adverse effect of alcohol on seizures
» sleep hygeine,
» the effect of missing a dose of medication,
» discontinuing the medication without advice of a doctor, and
» family planning is important in women of child-bearing potential as
anticonvulsants, especially valproate, can be teratogenic. Note that
there are important drug-drug interactions between hormonal
contraceptive (except DMPA) and several anticonvulsant medicines
(carbamazepine, phenobarbital, phenytoin).
» Patients with uncontrolled seizures should avoid driving and operating
machinery until they have been seizure free. Physician to provide
guidance.
2015
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NEUROLOGICAL DISORDERS
MEDICINE TREATMENT
The aim is to use monotherapy, i.e. a single anticonvulsant, progressively
increasing the dose until the seizures are controlled or clinically important
side effects occur.
If the initial medication fails to achieve satisfactory control with optimal
dosages, or causes unacceptable adverse effects, then a second medicine
may be started. The first drug should be continued for 2 weeks and then
gradually reduced over 6– 8 weeks until stopped. If the second drug fails,
and alcohol and poor adherence are excluded, then combination therapy
may be required. Refer patients for specialist investigation.
Patients with a history of myoclonic seizures or typical absence seizures
should preferably be treated with valproate, as those seizures may be
aggravated by the use of either phenytoin or carbamazepine.
Routine therapeutic drug monitoring is not useful except:
» To confirm toxicity in a symptomatic patient.
» To confirm poor adherence.
» With poor control despite good self reported adherence.
Partial seizures or generalised tonic clonic seizures
The choice between therapeutic agents must be made on the acceptability
of side effects and how the number of doses influences lifestyle.

Carbamazepine, oral.
o Start with 100 mg 12 hourly.
o Increase by 100–200 mg/day at weekly intervals according to
seizure control and adverse events.
ix
o Usual maximal dose: 600 mg 12 hourly.
LoE:III
OR
Lamotrigine, oral.
o 25 mg daily for 2 weeks, then 50 mg daily for 2 weeks.
o Thereafter, increase by 50 mg every 2 weeks according to
response.
o Usual maintenance dose: 100–200 mg daily as a single dose.
OR
LoE:III
Phenytoin, oral, 4.5–5 mg/kg (lean body mass) daily.
o Usual starting dose in an adult male: 300mg once daily.
o Dose changes above 300 mg should be done only in no more than
50 mg increments at intervals no shorter than 2 weeks.
LoE:III
For patients not stabilised on or who do not tolerate the above medications:

Valproate, oral.
o Usual starting dose: 200–300 mg 12 hourly.
o Increase, as required, every 2 weeks to a maximum daily dose of
1.2 g 12 hourly.
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Phenytoin, phenobarbitone and carbamazepine are potent enzyme
inducing agents and should be used with caution with other medicines
metabolised by the liver, especially warfarin, ARVs, progestin subdermal
implants and oral contraceptives.
Other epilepsy types
Manage in consultation with a specialist.
Specifically, juvenile myoclonic epilepsy is best controlled with valproate
initially, and absence seizures with valproate or lamotrigine.
HIV-infected individuals on ARVs
Phenytoin, phenobarbital and carbamazepine are enzyme inducing antiepileptic medicines. Due to potential drug interactions with antiretroviral
drugs, switch patients on these anti-epileptics to lamotrigine or valproate.

Lamotrigine, oral.
o 25 mg daily for 2 weeks, then 50 mg daily for 2 weeks.
o Thereafter, increase by 50 mg every 2 weeks according to
response.
o Usual maintenance dose: 100–200 mg daily, as a single dose or 12
hourly.
Note: The metabolism of lamotrigine is induced by lopinavir/ritonavir and
atazanavir/ritonavir. The dose of lamotrigine may need to be increased when
patients are switched to a lopinavir/ritonavir- or atazanavir/ritonavir containing regimen.
OR
Valproate, oral.
o Usual starting dose: 200–300 mg 12 hourly.
o Increase, as required, every 2 weeks to a maximum dose of 1200
mg 12 hourly.
Add on therapy to valproate:

Lamotrigine, oral.
o Start with 25 mg daily on alternate days for 2 weeks, increasing to
25 mg daily for 2 weeks.
o Thereafter increase by 25–50 mg every 2 weeks according to
response.
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Lamotrigine dose titration
x
LoE:III
Status epilepticus:
See section 14.3.1: Status Epilepticus.
Pregnancy
Optimal control of epilepsy on a single agent is the best management.
Do not initiate valproate during pregnancy, as it is associated with a
higher teratogenic potential than the other first line agents
Before pregnancy is considered, folate supplementation:

Folic acid, oral, 5 mg daily.
o Pregnancy alters drug levels, adjust dose according to levels.
Prophylaxis in head trauma
Phenytoin may be of benefit during initial period following significant head
trauma.

Phenytoin, IV, 20 mg/kg diluted in sodium chloride 0.9% (not dextrose)
administered not faster than 50 mg/minute preferably with cardiac
monitoring.
o If arrhythmias occur, interrupt the infusion temporarily and
reintroduce slowly.
o Continue with, IV, 5 mg/kg/day (300 mg daily for most adults).
xi
LoE:II
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REFERRAL
»
»
»
»
All new onset epileptics for neuro-imaging, if unavailable locally.
Epileptics who are poorly controlled on adequate treatment.
For consideration of combination therapy.
Epilepsy with unexplained neurological symptoms or signs.
14.3.1 STATUS EPILEPTICUS
G41
DESCRIPTION
A seizure lasting > 5 minutes or recurrent seizures without recovery to
baseline between episodes.
GENERAL MEASURES
Start treatment immediately. Do not wait for results of special investigations.
Secure the airway.
Check serum glucose, and treat if hypoglycaemic.
Check for hyponatraemia or uraemia and measure anticonvulsant levels if
the patient is on therapy.
Consider poisoning, e.g. isoniazid, theophylline, tricyclic antidepressants,
cocaine.
MEDICINE TREATMENT
Seizures should be stopped promptly as prolonged seizures can cause
permanent brain damage. Aim for definitive control within 60 minutes of onset.
INITIAL TREATMENT

Lorazepam, IV/IM, 4 mg, repeat after 5–10 minutes if necessary.
OR
Diazepam, IV, 10 mg, not faster than 2 mg/minute,
repeat after 5–10 minutes if necessary.
OR
Clonazepam, IV, 2 mg, repeat after 5–10 minutes if
necessary.
OR
Midazolam, IM/IV 10 mg, repeat after 5–10 minutes if
necessary.
OR
Midazolam buccal, 10 mg using the parenteral
formulation.
LoE:III
LoE:III
LoE:III
xii
LoE:I
LoE:III
AND

Phenytoin, IV, 20 mg/kg diluted in sodium chloride 0.9% (not dextrose)
administered not faster than 50 mg/minute preferably with cardiac
monitoring.
o If arrhythmias occur, interrupt the infusion temporarily and
2015
14.10
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NEUROLOGICAL DISORDERS
reintroduce slowly.
Seizures continuing after 30 minutes
Intubate and ventilate patient.

Thiopental, IV, 4 mg/kg, followed by 50 mg bolus every 2–3 minutes to
control seizures.
o Maintenance dose: 1–5 mg/kg/hour.
o Beware of hypotension.
o Once seizures controlled for 24 hours, wean off thiopental by
decreasing the dose by 1 mg/kg every 12 hours.
xiii
OR
LoE:III
Propofol, IV, 3mg/kg/dose as a bolus
o
Maintenance dose: 30–100 mcg/kg/minute.
xiv
LoE:I
Higher initial maintenance doses of phenytoin may be needed in patients
who have had thiopental. Doses should be guided by daily therapeutic drug
monitoring until phenytoin levels have stabilised after thiopental has been
weaned off.
MAINTENANCE THERAPY
If seizures are controlled:

Phenytoin, IV/oral, 300 mg daily.
o First maintenance dose should be no more than 12 hours after the
loading dose.
LoE:III
Clinical signs that seizures are controlled are autonomic
stability and the absence of abnormal movement.
Long term maintenance therapy: See section 14.3: Epilepsy.
14.4 HEADACHE AND FACIAL PAIN SYNDROMES
14.4.1 MIGRAINE
G43
DESCRIPTION
Episodic headache, usually focal in nature, which may occur with or without
an aura. It is usually accompanied by nausea and/or vomiting. Several
variants of migraine also occur.
GENERAL MEASURES
Reassure patient that this is a benign condition.
Attempt to identify any precipitating factors or food allergies from the history
(although this is usually unrewarding), and try to diminish patterns of tension.
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NEUROLOGICAL DISORDERS
MEDICINE TREATMENT
Acute treatment
Initiate therapy during the migraine attack or at the onset of the headache.
Analgesics, e.g.:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
OR

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg immediately then 8 hourly with meals, if needed.
If severe and not responding to therapy above:
 Morphine, IM, 3–5 mg as a single dose, then further boluses of 1–2
mg/minute to a total maximum dose of 10 mg and monitor closely. (See
Appendix II, for individual dosing and monitoring for response and
toxicity).
For nausea:

Metoclopramide, oral/IM, 10 mg 8 hourly.
Prophylaxis
Regular, daily, prophylactic therapy is advised if:
» attacks are frequent, i.e. more than 2–3 per month, or
» severe, causing a significant amount of disability, or
» attacks are long lasting.
Also consider for patients who tolerate therapy for acute attacks poorly.

Amitriptyline, oral, 10–25 mg at bedtime.
o Titrate dose up to adequate response.
o More than 75–150 mg as a single bedtime dose is seldom required.
OR
Carbamazepine, oral.
o Start with 100 mg 12 hourly.
o Increase every two weeks up to a maximum of 400 mg 12 hourly.
Note: Only about half of patients will respond to one of these agents and this
response may take 1– 2 months to occur.
14.4.2 CLUSTER HEADACHE
G44.0
DESCRIPTION
Repetitive episodes of excruciating headache typically of short duration (up to
2 hours) in clusters for weeks to months at a time. Typically the headache is of
sudden onset, unilateral during the specific cluster, and quickly reaches a
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climax. Associated redness of the eye with lacrimation and rhinorrhoea occurs.
MEDICINE TREATMENT
Oxygen inhalation may abort some episodes.
Analgesics are ineffective.
To induce rapid remission in patients with episodic cluster headache:

Prednisone, oral, 40 mg daily for 5–10 days.
o Tapering is not necessary when the above duration is used.
OR

Verapamil, oral, 40 to 80 mg 12 hourly.
REFERRAL
Inadequate response to treatment.
14.4.3 TRIGEMINAL NEURALGIA
G50.0
DESCRIPTION
Severe, very short lived stabs of facial pain in the sensory trigeminal
distribution. It is important in the diagnostic workup to exclude intracranial
mass lesions, which may impinge on the trigeminal nerve.
MEDICINE TREATMENT

Carbamazepine, oral, 100 mg 12 hourly, initial dose.
o Increase dose slowly. Doses of up to 1 200 mg daily may be
required.
o After exacerbation, reduce to maintenance dose of 400–800 mg daily.
REFERRAL
»
»
Neuro-imaging, if not available locally.
Poor response to single drug therapy.
14.4.4 TENSION HEADACHE
G44.2
DESCRIPTION
Headache over the back of the head, but sometimes over the entire head,
described as a tight band around the head, usually worse in the afternoon.
GENERAL MEASURES
Consider use of relaxation techniques.
The importance of this diagnosis is the exclusion of other, more sinister
conditions.
Exclude analgesia overuse headache.
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NEUROLOGICAL DISORDERS
MEDICINE TREATMENT

Amitriptyline, oral, 10–75 mg at night.
REFERRAL
»
»
Atypical pain, suggestive of alternate diagnosis.
Poor response to therapy.
14.4.5 IDIOPATHIC INTRACRANIAL HYPERTENSION
(PSEUDOTUMOUR CEREBRI)
G93.2
DESCRIPTION
Patients present with symptoms (chronic headache and sometimes eventual
visual loss due to persistent papilloedema) and signs (papilloedema) of raised
intracranial pressure in the absence of any structural intracranial abnormality
or abnormal CSF composition.
Diagnosis
All patients should have neuro-imaging (CT scan).
» If this is normal, i.e. the absence of structural lesions or hydrocephalus,
perform a lumbar puncture.
» Diagnosis is confirmed by the presence of raised CSF pressure > 20 cm H20.
GENERAL MEASURES
Not all patients require definitive treatment.
Regular monitoring of visual fields is crucial.
Weight loss.
Repeated lumbar punctures.
Consider surgery if there is progression of visual defects, despite medical
therapy, visual loss at onset or severe papilloedema.
Stop medicines known to be associated with benign intracranial
hypertension (e.g. doxycycline, amiodarone, levodopa, corticosteroids).
MEDICINE TREATMENT
All patients need to be discussed with a specialist.
For visual involvement, persistent headaches, or severe papilloedema:

Acetazolamide, oral, 1–2 g daily.
OR
Furosemide, oral, 40 mg daily.
REFERRAL
»
»
»
For neuro-imaging, if not available locally.
Visual symptoms or deterioration of visual fields for opthalmology
evaluation.
Patients not responding to therapy or in need of surgical management.
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14.5 INFECTIOUS AND PARASITIC CONDITIONS
14.5.1 MENINGITIS
G00/G01*/G02.1*
*N. meningitidis and H. influenzae Type B are notifiable diseases.
DIAGNOSIS
Lumbar puncture for chemistry and bacteriology or fungal investigation
should be done in all cases, if safe.
Computed tomography needs to be done before lumbar puncture in patients
with:
» focal neurological signs,
» new seizures,
» papilloedema, or
» reduced level of consciousness.
In cases where lumbar puncture is delayed or cannot be done (e.g.
uncontrolled significant bleeding tendency), commence empiric antibiotic
therapy after taking samples for blood cultures. Attempt the lumbar puncture
later, if possible.
GENERAL MEASURES
Observe patient closely with regular monitoring of vital signs and
neurological state.
Pay close attention to nutritional and hydration status.
Nurse patients in a quiet, semi-dark surrounding.
In uncomplicated bacterial meningitis, repeated lumbar punctures are of no
benefit.
Prompt initiation of antibiotic therapy is associated with improved outcomes.
MEDICINE TREATMENT
All patients require sufficient analgesia:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND/OR

Ibuprofen, oral, 400 mg then 8 hourly with meals, if needed.
AND/OR
 Morphine, IM/IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Antibiotic therapy
Empiric therapy for bacterial meningitis, until sensitivity results are available:
xv
LoE:III

Ceftriaxone, IV, 2 g 12 hourly for 10 days.
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NEUROLOGICAL DISORDERS
Adjunctive corticosteroids have not been demonstrated to be of value.
Meningococcal meningitis
For confirmed meningococcal disease only:

Benzylpenicillin (penicillin G), IV, 20–24 million units daily in 4–6 divided
doses for one week.
Eradicate nasopharyngeal carriage with a single dose of ciprofloxacin 500
mg after completing course of benzylpenicillin (see below). This is not
required if the patient was treated with ceftriaxone for ≥ 24 hours.

Ciprofloxacin, oral, 500 mg immediately as a single dose.
Prophylaxis of contacts:
Only for close household contacts.
Only healthcare workers who resuscitate patients before they received
appropriate treatment should receive prophylaxis.

Ciprofloxacin, oral, 500 mg immediately as a single dose.
Pneumococcal meningitis
This organism may be associated with other respiratory disease or CSF
leaks.
If sensitive to penicillin:

Benzylpenicillin (penicillin G), IV, 20–24 million units daily in 4–6 divided
doses for 10 days.
If resistant to penicillin:

Ceftriaxone, IV, 2 g 12 hourly for at least 10 days.
Haemophilus influenzae

Ceftriaxone, IV, 2 g 12 hourly for 10 days.
Severe penicillin allergy:

Vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20
mg/kg/dose 12 hourly. (See Appendix II for guidance on prescribing and
monitoring).
AND

Rifampicin, oral, 600 mg 12 hourly.
Note: Consult a microbiologist/infectious diseases specialist.
Tuberculous meningitis
CSF findings are extremely variable. Generally lymphocytes predominate,
however, polymorphs may initially predominate in about a third of patients.
Protein is usually > 1 g/L and glucose is usually low.
In cases where the differential diagnosis between bacterial and tuberculous
meningitis is in doubt, lumbar puncture should be repeated 2-3 days later
while still on ceftriaxone. If the aetiology is bacterial, considerable
improvement in CSF findings may be expected, but with untreated
2015
14.16
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NEUROLOGICAL DISORDERS
tuberculous meningitis the cell counts and protein levels will be the same or
higher; and the glucose level will be the same or lower.
Standard combination tuberculosis therapy according to National protocol.
See section 16.9: Tuberculosis, Pulmonary.
Duration of therapy: 9 months.

Dexamethasone, IV, 12 mg 12 hourly.
xvi
Followed with:
LoE:I

Prednisone, oral, 120 mg daily.
o After 1 week, taper dose over next 6 weeks. (Refer to page xxvii for
an example of a dose reduction regimen).
Cryptococcal meningitis
HIV-infected patients, see section 10.2.4: Cryptococcosis. In HIV infection
the aim is to suppress the infection until immune restoration occurs with
antiretroviral therapy.
In HIV-uninfected patients the aim is to cure the infection.
Initial therapy:

Amphotericin B, IV, 1 mg/kg daily.
o Ensure adequate hydration to minimise nephrotoxicity. (See
Appendix II for preventing, monitoring and management of toxicity).
o Duration of initial IV therapy:
- Treat intravenously for 6 weeks, provided that there are no
neurological complications and follow up CSF culture at 2
weeks is negative (India ink or Cryptococcus Latex
Agglutination Test (CLAT) may still be positive).
- In patients with neurological complications or persistent
positive culture: Consider lengthening the initial phase of
therapy to 8 weeks in consultation with a specialist.
AND

Fluconazole, oral, 800 mg daily.
Maintenance therapy:

Fluconazole, oral, 200 mg daily for ≥ 6 months, in consultation with a
specialist.
Follow all patients closely for relapses.
xvii
LoE:III
Therapeutic lumbar puncture:
This should be considered as the intracranial pressure is often elevated with
a communicating hydrocephalus.
See section 10.2.4: Cryptococcosis.
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14.5.2 VIRAL MENINGOENCEPHALITIS
A86
DESCRIPTION
Patients present with headache, neck stiffness, and encephalitic symptoms
which may include fever, personality or behavioural changes, hallucinations
and seizures. Lumbar puncture typically shows mildly elevated protein,
normal glucose and mildly raised cells (< 500), mainly lymphocytes (early on
polymorphs may predominate). Most cases do not require specific therapy,
other than analgesia.
MEDICINE TREATMENT
Analgesia, i.e.:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4
doses per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND

NSAIDs, e.g.:

Ibuprofen, oral, 400 mg immediately then 8 hourly with meals, if needed.
xviii
LoE:III
OR

Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
Herpes simplex encephalitis
Clinical features are fever, change in behaviour and seizures, which may be
either focal or generalised.
Evidence of mucocutaneous involvement is usually not present. Lumbar
puncture shows the above features of viral meningoencephalitis, but in this
condition may be additionally haemorrhagic in nature. A medial temporal
focus on EEG or MRI/CT neuro-imaging is strongly supportive of the
diagnosis, and positive HSV PCR test on CSF is diagnostic.

Aciclovir, IV, 10 mg/kg 8 hourly for 21 days.
o Start therapy as early as possible, i.e. before results are available.
o A negative herpes PCR usually excludes the diagnosis unless the
specimen was taken within 72 hours of onset of symptoms, when
false negatives have been described.
Treat seizures appropriately with phenytoin/carbamazepine. See section
14.3: Epilepsy. All suspected cases of herpes encephalitis should be
discussed with a specialist.
2015
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NEUROLOGICAL DISORDERS
REFERRAL
»
»
»
For neuro-imaging: patients not responding or worsening in condition,
i.e. decrease in consciousness and cranial nerve palsies, despite
appropriate therapy.
This is especially urgent in patients with tuberculous meningitis, who
may develop hydrocephalus and require an urgent shunting procedure.
Patients with shunts.
14.5.3 MENINGOVASCULAR SYPHILIS
A52.1
DIAGNOSIS
Lumbar puncture typically shows lymphocytosis with mildly elevated protein
and low/normal glucose.
Serum syphilis serology: a negative TPHA excludes the diagnosis; RPR may
be negative.
CSF syphilis serology: VDRL in CSF is often of low titre, and may be
negative; a negative CSF FTA-abs excludes the diagnosis of neurosyphilis.
MEDICINE TREATMENT

Benzylpenicillin (penicillin G), IV, 20 million units daily in 4–6 divided
doses for 10 days.
LoE:III
Severe penicillin allergy:
Refer for consideration of desensitisation and subsequent treatment with
benzylpenicillin at a referral centre.
14.5.4 BRAIN ABSCESS
G07*
DIAGNOSIS
Patient may present with focal neurological signs and signs of infection.
Neurological signs may not always be prominent. Neuro-imaging usually
confirms diagnosis. Patients may have concomitant infection of ears,
paranasal sinuses or lower respiratory tract.
MEDICINE TREATMENT
Empiric antibiotic therapy

Ceftriaxone, IV, 2 g 12 hourly.
AND

Metronidazole, oral, 400 mg 8 hourly or IV, 500 mg 8 hourly.
Adjust according to antimicrobial sensitivity after surgical drainage.
REFERRAL
All, as patients require urgent neurosurgery opinion and treatment.
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14.5.5 ANTIMICROBIAL USE IN PATIENTS WITH HEAD
INJURIES
S06.00
MEDICINE TREATMENT
Basal skull fractures
Antibiotic prophylaxis is not indicated.
Penetrating brain injuries
Antibiotics are given for therapy.
rd

3 generation cephalosporin, e.g.:

Ceftriaxone, IV, 2 g 12 hourly for 7 days.
LoE:III
14.5.6 NEUROCYSTICERCOSIS
B69.0
DIAGNOSIS
Patients may present with seizures and/or focal neurological deficit. Typical
cystic lesions are seen on neuro-imaging. Old calcified lesions are inactive
and do not require treatment.
GENERAL MEASURES
Health education.
Surgery for treatable ventricular blockage or spinal or intraocular cysts.
MEDICINE TREATMENT
For active or viable cysts only:

Albendazole, oral, 12 hourly for 8 days.
o > 60 kg: 400 mg.
o < 60 kg: 7.5 mg/kg to a maximum of 800 mg daily.
o Do not use in pregnancy.
AND

Prednisone, oral, 60 mg daily for 8 days.
xix
LoE:II
xx
Anticonvulsants, if required.
See section 14.3: Epilepsy.
LoE:II
14.6 MOVEMENT DISORDERS
G25.9
DESCRIPTION
Abnormalities of movement/initiation of movement, divided into those with
reduction of movement (hypokinesia or bradykinesia), or those with
excessive movements (hyperkinesia).
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14.6.1 PARKINSONISM
G20
DESCRIPTION
Parkinsonism is a syndrome characterised by tremor, rigidity, bradykinesia
and postural disturbances. It may be primary, i.e. Parkinson’s disease, or
secondary, i.e. drug-induced or due to uncommon disorders that may initially
resemble Parkinson’s disease.
The objective of treatment is to:
» minimise disabling symptoms,
» prevent complications and avoid serious drug-induced side effects, and
» exclude secondary forms.
GENERAL MEASURES
General supportive therapy and advice about lifestyle modification,
physiotherapy and occupational therapy.
MEDICINE TREATMENT
Note: Set therapeutic targets so that the patient is functioning as well as
possible.
PRIMARY PARKINSONISM
Bradykinesia, rigidity and postural disturbance:

Carbidopa/levodopa, 25/100 mg, oral, ½ tablet 8 hourly.
o Increase dose in consultation with a specialist.
If optimal control has not been achieved, consider an alternative diagnosis or
changing to a medicine containing a higher dose of levodopa:

Carbidopa/levodopa 25/250 mg. Specialist initiated.
Drug-induced parkinsonism:
Anticholinergics have a very small role in this setting and should be used
with caution.

Anticholinergic agent, e.g.:

Orphenadrine, oral, 50 mg 8 hourly.
xxi
LoE:III
Tremor only:

Consider anticholinergic agent, e.g.:

Orphenadrine, oral, 50 mg 8 hourly. Increase gradually according to
clinical response or maximum dose of 400mg daily
o Usual dose: 150–250 mg daily.
Acute dystonic reaction:
Usually follows administration of
metoclopramide and phenothiazines.
2015
dopamine-antagonistic
drug,
e.g.
14.21
CHAPTER 14


NEUROLOGICAL DISORDERS
Anticholinergic agent, e.g.:
Biperiden, IM/IV, 2 mg.
o Repeat as necessary.
OR
Promethazine, deep IM, 25–50 mg.
o In the elderly 25 mg.
LoE:III
REFERRAL
»
»
»
No improvement or poor control with treatment.
Increasing on/off phenomenon.
Dyskinesias.
14.6.2 ESSENTIAL TREMOR
G25.0
GENERAL MEASURES
Exclude and manage alternate causes, such as drugs, thyrotoxicosis,
hyperadrenergic states and psychiatric disorders. Occasionally a patient
may present with essential tremor and an additional neurological condition,
which may make the diagnosis difficult.
MEDICINE TREATMENT
If tremor is severe and interfering with normal daily activity:

Propranolol, oral,
o
Start at 20 mg daily and titrate as needed up to 80 mg 8 hourly.
xxii
o
Monitor BP.
LoE:III
14.6.3 CHOREA
G25.5
DESCRIPTION
Involuntary random, irregular movements.
Aetiology is classified as:
» primary – Huntington’s chorea, benign hereditary chorea and others; or
» secondary – due to Sydenham’s chorea, vascular pathology, metabolic,
endocrine and infective conditions, amongst others.
MEDICINE TREATMENT
To be prescribed by a specialist only.

Haloperidol, oral, 0.5–5 mg 2–3 times daily.
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14.7 NEUROPATHY
G62
DESCRIPTION
Defective functioning of nerves, which may involve both peripheral nerves
(peripheral neuropathy) and cranial nerves. Different patterns are noted, i.e.
polyneuropathy, mononeuritis multiplex and mononeuropathy, each of which
may be caused by axonal degeneration or demyelination or a combination of
the above. Clinical features may be predominantly of a sensory, sensorimotor
or motor nature.
Important causes of neuropathy include:
» alcohol,
» diabetes,
» HIV infection,
» thiamine deficiency, vitamin B12 deficiency, (although the latter more
commonly presents as subacute combined degeneration of the cord.)
» drugs (e.g. isoniazid, stavudine, metronidazole, amiodarone)
» acute inflammatory demyelinating polyradiculoneuropathy (AIDP – also
known as Guillain-Barrè syndrome),
» chronic inflammatory demyelinating polyradiculoneuropathy (CIDP),
» acute porphyrias
GENERAL MEASURES
If there is a history of rapid progression, particularly in patients with features
suggestive of AIDP, (e.g. over ≤ 7 days) admit the patient and monitor vital
capacity carefully with spirometry, as intubation and ventilatory support may
be required.
Manage the cause where possible.
Specialised nursing care and dedicated physiotherapy may be indicated. If not
managed appropriately, chronic cases may develop contractures, weakness
affecting gait, develop chronic bedsores and become wheel chair-bound.
MEDICINE TREATMENT
Most cases respond to management of the underlying disease process or
removal of the aetiological agent.
Neuropathic pain (i.e. pain due to a disease or injury of the central or
peripheral nervous system)

Amitriptyline, oral, 25–75 mg daily.
OR
Carbamazepine, oral, 200–1200 mg daily in divided doses.
Isoniazid–induced polyneuropathy

Pyridoxine, oral 75 mg daily for 3 weeks.
o Follow with 25–50 mg daily.
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Post-herpes zoster neuropathy
Note: Aciclovir is not beneficial in treating this condition.

Amitriptyline, oral, 25–75 mg daily.
xxiii
AND/OR

Carbamazepine, oral 200–1200 mg daily dose in divided doses.
o Beware of possible drug interactions in patients on ART.
LoE:I
Bells palsy
Prevention of corneal ulceration is important. Consider lubrication (see
section 18.9; Eye Chapter), eye patch and chewing.
In patients presenting within 72 hours of onset of symptoms of a Bells palsy
who are HIV uninfected and have no evidence of local herpes zoster or
suppurative otitis media, corticosteroids improve the probability of facial
recovery at 3 months (83% vs. 63.6%), although even without treatment over
80% will recover by 9 months. The addition of aciclovir is not of proven
benefit.

Prednisone, oral, 50 mg daily for 10 days.
xxiv
LoE:I
REFERRAL
»
»
Electrophysiological studies may be needed in the diagnostic
assessment, although many common causes do not warrant specialist
investigations, e.g. polyneuropathies due to diabetes mellitus, HIV,
drugs, and alcohol. These cases may initially be managed locally, with
referral of non-responding or atypical cases.
Gullain-Barré Syndrome: referral criteria are progressive, extensive
paralysis with impending respiratory failure, bulbar palsy and swallowing
problems, and aspiration, as well as for diagnostic confirmation.
14.8 ACUTE MYELOPATHY
G95.9
DESCRIPTION
Patients present with a sudden onset of paraparesis, with associated
sensory loss, i.e. a sensory level may be found. Incontinence and autonomic
instability may be present.
Note: Do not perform a lumbar puncture, until obstructive lesions of the
spinal cord have been excluded clinically or radiologically.
REFERRAL
All patients for urgent imaging.
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14.9 MULTIPLE SCLEROSIS
G35
DESCRIPTION
A demyelinating disease of the central nervous system, characterised by
episodes of unifocal or multifocal neurological dysfunction. Diagnosis is
confirmed by imaging. The CSF may show oligoclonal bands and raised IgG
index. Recovery between acute flares of illness is common, although a
general stepwise deterioration from baseline is usually found.
Consult with neurologist for diagnosis and treatment.
REFERRAL
All patients.
14.10 MYASTHENIA GRAVIS
G70.0
DESCRIPTION
Consider this in patients with new onset weakness and fatiguability.
particularly involving the eyes and the swallowing muscles.
MEDICINE TREATMENT
Discuss both diagnosis and treatment with a specialist.

Pyridostigmine, oral, 60 mg 5 times daily.
xxv
LoE:III
Corticosteroids and azathioprine should only be used in consultation with a
specialist.
14.11 OEDEMA, CEREBRAL
G93.6
DESCRIPTION
Swelling of brain parenchymal tissue, due to vasogenic, cytotoxic and
osmotic causes. Only the vasogenic causes, such as brain tumours and
inflammation, respond to corticosteroids.
14.11.1 BRAIN OEDEMA DUE TO TUMOURS AND
INFLAMMATION
G93.6
GENERAL MEASURES
Supportive management. See section 14.1.1: Stroke.
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MEDICINE TREATMENT
Treat the underlying cause. This is especially important with brain oedema
associated with systemic conditions, such as electrolyte disturbances and
organ failure.
Patients with primary brain tumours or brain metastases should be
considered for specific treatment of the tumour, which includes surgery
and/or radiotherapy.

Dexamethasone, IV, 4 mg 6 hourly, initially.
OR
Betamethasone, oral/IV, 4 mg 6 hourly.
o Discontinue if no response has occurred after 48 hours.
o Taper dose according to response and duration of therapy.
14.11.2 BRAIN OEDEMA DUE TO TRAUMATIC INJURY
S06.1
GENERAL MEASURES
Refer patient for neurosurgical opinion, if indicated.
Supportive management. See section 14.1.1: Stroke.
Note: DVT prophylaxis with heparin may be contraindicated owing to risk of
increased bleeding.
The following measures should be used in patients with raised intracranial
pressure:
» head elevation and position,
» airway and ventilation control,
» sedation and analgesia,
» control of fever,
» control of hypertension, and
» prevention of seizures.
Currently, no evidence supports the use of hyperventilation in this setting.
MEDICINE TREATMENT
For raised intracranial pressure, pending a definitive neurosurgical
procedure only:

Mannitol 15–25%, IV, 0.25–1 g/kg administered over 30–60 minutes.
o Monitor neurological response and urine output.
o Beware of hypovolaemia and electrolyte disturbances, especially
hypokalaemia.
Note: Corticosteroids used in this setting have a harmful effect.
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References:
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Aspirin: Sandercock PA, Counsell C, Tseng MC, Cecconi E. Oral antiplatelet therapy for acute ischaemic stroke.
Cochrane Database Syst Rev. 2014 Mar 26;3:CD000029. http://www.ncbi.nlm.nih.gov/pubmed/24668137
ii
Simvastatin 10 mg: Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D. The relationship between reduction
in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated metaanalysis. ClinTher. 2009 Feb;31(2):236-44. http://www.ncbi.nlm.nih.gov/pubmed/ 19302897
Simvastatin 10 mg: Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on
serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev
Cardiol. 2013 Aug;20(4):658-70. http://www.ncbi.nlm.nih.gov/pubmed/23529608
Simvastatin 10 mg: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein
cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun
28;326(7404):1423. http://www.ncbi.nlm.nih.gov/pubmed/12829554
Simvastatin 10 mg: Contract circular HP09-2014SD. http://health.gov.za/
iii
Warfarin: Lansberg MG, O'Donnell MJ, Khatri P, Lang ES, Nguyen-Huynh MN, Schwartz NE, Sonnenberg FA,
Schulman S, Vandvik PO, Spencer FA, Alonso-Coello P, Guyatt GH, Akl EA; American College of Chest
Physicians. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines. Chest. 2012 Feb;141(2 Suppl):e601S-36S. http://www.ncbi.nlm.nih.gov/pubmed/22315273
iv Long-acting calcium channel blocker/Thiazide diuretic: Bath PM, Krishnan K. Interventions for deliberately
altering blood pressure in acute stroke. Cochrane Database Syst Rev. 2014 Oct 28;10:CD000039.
http://www.ncbi.nlm.nih.gov/pubmed/25353321
Long-acting calcium channel blocker/Thiazide diuretic: He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS, Tong
W, Liu C, Xu T, Ju Z, Peng Y, Peng H, Li Q, Geng D, Zhang J, Li D, Zhang F, Guo L, Sun Y, Wang X, Cui Y, Li Y,
Ma D, Yang G, Gao Y, Yuan X, Bazzano LA, Chen J; CATIS Investigators. Effects of immediate blood pressure
reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial.
JAMA. 2014 Feb 5;311(5):479-89. http://www.ncbi.nlm.nih.gov/pubmed/24240777
v
Warfarin: SAMF, 2014.
vi
Aspirin: Thijs V, Lemmens R, Fieuws S. Network meta-analysis: simultaneous meta-analysis of common
antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J. 2008 May;29(9):1086-92.
http://www.ncbi.nlm.nih.gov/pubmed/18349026
vii
Corticosteroids: Botelho RV, Daniel JW, Boulosa JL, et al. Effectiveness of methylprednisolone in acute spinal
cord injury– a systematic review of randomized controlled trials. Rev Assoc Med Bras 2009; 2010; 56(6): 729-37.
Corticosteroids: Roberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G, Cottingham R, Svoboda
P, Brayley N, Mazairac G, Laloë V, Muñoz-Sánchez A, Arango M, Hartzenberg B, Khamis H, Yutthakasemsunt S,
Komolafe E, Olldashi F, Yadav Y, Murillo-Cabezas F, Shakur H, Edwards P; CRASH trial collaborators. Effect of
intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC
CRASH
trial):
randomised
placebo-controlled
trial.
Lancet.
2004
Oct
9-15;364(9442):1321-8.
http://www.ncbi.nlm.nih.gov/pubmed/15474134
viii
Thiamine oral/IM: Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and
treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev. 2013 Jul
1;7:CD004033. http://www.ncbi.nlm.nih.gov/pubmed/23818100
Thiamine oral/IM: PHC STGs and EML, 2014. http://www.health.gov.za/
ix
Carbamazepine: Gigli GL, Placidi F, Diomedi M, Maschio M, Silvestri G, Scalise A, Marciani MG. Nocturnal
sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: changes after treatment with
controlled-release carbamazepine. Epilepsia. 1997 Jun;38(6):696-701.
http://www.ncbi.nlm.nih.gov/pubmed/9186252
x
Lamotrigine: SAMF, 2014.
Lamotrigine: NICE Clinical Guideline 137. The epilepsies: the diagnosis and management of the epilepsies in
adults and children in primary and secondary care. Issued Jan2012; modified Jan 2015.
http://guidance.nice.org.uk/cg137
xi
Phenytoin: Chang BS, Lowenstein DH. Practice parameter: Antiepileptic drug prophylaxis in severe traumatic
brain injury Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology
2003;60:10-16. http://www.ncbi.nlm.nih.gov/pubmed/12525711
Phenytoin: Young B, Rapp RP, Norton JA, Haack D, Tibbs PA, Bean JR. Failure of prophylactically
administered phenytoin to prevent early posttraumatic seizures. J Neurosurg 1983;58:231–235.
http://www.ncbi.nlm.nih.gov/pubmed/6848680
xii
Midazolam IM/IV: Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT
Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb
16;366(7):591-600. http://www.ncbi.nlm.nih.gov/pubmed/22335736
xiii
Thiopental: Minicucci F, Muscas G, Perucca E, Capovilla G, Vigevano F, Tinuper P. Treatment of status
epilepticus in adults: guidelines of the Italian League against Epilepsy. Epilepsia. 2006;47 Suppl 5:9-15.
http://www.ncbi.nlm.nih.gov/pubmed/17239099
Thiopental: NICE Clinical Guideline 137. The epilepsies: the diagnosis and management of the epilepsies in
adults and children in primary and secondary care. Issued Jan2012; modified Jan 2015.
http://guidance.nice.org.uk/cg137
xiv
Propofol: Prabhakar H, Bindra A, Singh GP, Kalaivani M. Propofol versus thiopental sodium for the treatment of
refractory
status
epilepticus.
Cochrane
Database
Syst
Rev.
2012
Aug
15;8:CD009202.
http://www.ncbi.nlm.nih.gov/pubmed/22895985
xv
Empiric antibiotic therapy: Proulx N, Fréchette D, Toye B, Chan J, Kravcik S. Delays in the administration of
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antibiotics are associated with mortality from adult acute bacterial meningitis. QJM. 2005 Apr;98(4):291-8.
http://www.ncbi.nlm.nih.gov/pubmed/15760921
Empiric antibiotic therapy: Koster-Rasmussen R, Korshin A, Meyer CN. Antibiotic treatment delay and outcome
in acute bacterial meningitis. J Infect. 2008 Dec;57(6):449-54. http://www.ncbi.nlm.nih.gov/pubmed/19000639
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Dexamethasone: Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis. Cochrane
Database Syst Rev. 2008 Jan 23;(1):CD002244. http://www.ncbi.nlm.nih.gov/pubmed/18254003
xvii
Amphotericin B: Southern African HIV Clinicians Society: Guideline for the prevention, diagnosis and
management of cryptococcal meningitis among HIV-infected persons:2013 update. S Afr J HIV Med 2013;14(2):7686. [Online][Accessed 8March2015] http://www.sajhivmed.org.za/index.php/hivmed/article/view/82
Fluconazole: Southern African HIV Clinicians Society: Guideline for the prevention, diagnosis and management
of cryptococcal meningitis among HIV-infected persons:2013 update. S Afr J HIV Med 2013;14(2):76-86.
[Online][Accessed 8March2015] http://www.sajhivmed.org.za/index.php/hivmed/article/view/82
xviii
Ibuprofen: SAMF, 2014.
xix
Albendazole: Abba K, Ramaratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis.
Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000215. http://www.ncbi.nlm.nih.gov/pubmed/20091504
Albendazole: Garcia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, Herrera G, Evans
CA, Gonzalez AE; Cysticercosis Working Group in Peru. A trial of antiparasitic treatment to reduce the rate of
seizures
due
to
cerebral
cysticercosis.
N
Engl
J
Med.
2004
Jan
15;350(3):249-58.
http://www.ncbi.nlm.nih.gov/pubmed/14724304
xx
Prednisone: Vazquez VA, Sotelo J. The course of seizures after treatment for cerebral cysticercosis. N Engl J
Med. 1992;327:696-701. http://www.ncbi.nlm.nih.gov/pubmed/1495522
xxi
Orphenadrine: SAMF, 2014.
xxii
Propanolol: Rajput AH, Rajput A. Medical treatment of essential tremor. J Cent Nerv Syst Dis. 2014 Apr
21;6:29-39. http://www.ncbi.nlm.nih.gov/pubmed/24812533
Propanolol: Jefferson D, Jenner P, Marsden CD. Relationship between plasma propranolol concentration and
relief of essential tremor. J Neurol Neurosurg Psychiatry. 1979 Sep;42(9):831-7.
http://www.ncbi.nlm.nih.gov/pubmed/501384
xxiii
Amitryptiline: Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and
fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008242.
http://www.ncbi.nlm.nih.gov/pubmed/23235657
Amitryptiline: McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic
pain. Anaesthesia. 1993 Apr;48(4):281-5. http://www.ncbi.nlm.nih.gov/pubmed/8494126
xxiv
Prednisone: de Almeida JR, Al Khabori M, Guyatt GH, Witterick IJ, Lin VY, Nedzelski JM, Chen JM. Combined
corticosteroid and antiviral treatment for Bell palsy: a systematic review and meta-analysis. JAMA. 2009 Sep
2;302(9):985-93. http://www.ncbi.nlm.nih.gov/pubmed/19724046
Prednisone: Numthavaj P, Thakkinstian A, Dejthevaporn C, Attia J. Corticosteroid and antiviral therapy for Bell's
palsy: a network meta-analysis. BMC Neurol. 2011 Jan 5;11:1. http://www.ncbi.nlm.nih.gov/pubmed/21208452
Prednisone: Sullivan FM, Swan IR, Donnan PT, Morrison JM, Smith BH, McKinstry B, Davenport RJ, Vale LD,
Clarkson JE, Hammersley V, Hayavi S, McAteer A, Stewart K, Daly F. Early treatment with prednisolone or
acyclovir in Bell's palsy. N Engl J Med. 2007 Oct 18;357(16):1598-607.
http://www.ncbi.nlm.nih.gov/pubmed/17942873
xxv
Pyridostigmine: SAMF, 2014.
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15.1 AGGRESSIVE DISRUPTIVE BEHAVIOUR IN ADULTS
R45.1
DESCRIPTION
Agitated and acutely disturbed patients, with or without a known psychiatric
condition.
Note: Many acute medical conditions and substance abuse can present with
agitation and aggressive behaviour.
GENERAL MEASURES
»
»
»
Ensure the safety of the patient and those caring for them.
Elderly and frail patients may be vulnerable to falls and further injury if
sedated.
Physical restraint should be used only when necessary to protect the
patient and others in an acute setting, and for as short a period of time
as possible, at all times monitoring the safety of the patient.
MEDICINE TREATMENT
Always use non-pharmacological de-escalation techniques first:
» Calm the patient.
» Manage in a safe environment.
» Ensure the safety of all staff members.
Offer oral treatment:

Benzodiazepines:

Lorazepam, oral, 4 mg, immediately.
OR
Clonazepam, oral, 2 mg, immediately.
OR
Diazepam, oral, 10 mg, immediately.
OR
Midazolam, oral or buccal, 15 mg, immediately.
i
LoE:II
ii
LoE:III
iii
LoE:III
iv
LoE:III
v
LoE:III
2015
15.1
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If oral treatment fails after 30–60 minutes,
OR
If the patient is placing themselves and others at significant risk:
Parenteral treatment:

Benzodiazepines:

Lorazepam, IM, 4 mg, immediately.
OR
Midazolam, IM, 15 mg immediately.
OR
Clonazepam, IM, 2 mg, immediately.
OR
Diazepam, IV, 10 mg, immediately.
o Repeat after 30–60 minutes if needed.
vi
LoE:II
vii
LoE:I
OR
Haloperidol, IM, 5 mg, immediately.
AND
Promethazine, deep IM, 25–50 mg.
viii
LoE:II
Repeat after 30–60 minutes if needed.
See the note regarding benzodiazepines in section 15.2: Confusional
states/delirium.
If haloperidol is unavailable, use chlorpromazine without promethazine:

Chlorpromazine, deep IM, 25–50 mg.
ix
o May be repeated as necessary 4 times in 24 hours.
LoE:III
If patient is known to suffer from schizophrenia and is not neuroleptic naive:
 Zuclopenthixol acetate, IM, 50–150 mg.
x
o Repeat after 2–3 days, if necessary.
LoE:III
If patient develops acute dystonia:

Anticholinergic agent, e.g.:

Biperiden, IM/IV, 2 mg.
o Repeat as necessary.
OR
Promethazine, deep IM, 25–50 mg.
o In the elderly 25 mg.
Repeated doses of high potency antipsychotics may lead to the development
of the life-threatening neuroleptic malignant syndrome, characterized by
hyperthermia, muscle rigidity, autonomic dysfunction, and alterations in
consciousness. Serum CK is typically markedly elevated. If suspected, stop
antipsychotic, and institute supportive care.
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PSYCHIATRIC DISORDERS
Always monitor vital signs of sedated patients:
» Vital signs: pulse, respiratory rate, blood pressure, temperature (If
concerned about respiratory depression, monitor with oximeter).
» Monitor every 5–10 minutes for the first hour, and then every 30 minutes
until the patient is ambulatory.
15.2 CONFUSIONAL STATES/DELIRIUM
F05.9
DESCRIPTION
Confusional states/delirium are characterised by altered consciousness,
accompanied by impairments in orientation to time and place and seldom to
person. Mental status may fluctuate. Disturbed behavior may be present,
e.g. agitation, hallucinations and paranoid ideation.
Note: Many acute medical emergencies can present as delirium, which may be
misdiagnosed as an acute psychosis.
GENERAL MEASURES
Control the acute disturbance.
Investigations need to be done to exclude or diagnose an underlying medical
problem, the treatment of which is the primary management.
MEDICINE TREATMENT
Treat underlying medical condition, if present.
Acute management
For agitated and acutely disturbed patient:

Haloperidol, IM, 5 mg.
o This can be repeated in 60 minutes, if required.
o Maximum dose: 10 mg within 24 hours.
o Monitor vital signs and beware of acute dystonia and neuroleptic
malignant syndrome.
o Dosing may vary according to clinical circumstances, e.g. lower doses
in the elderly or where HIV infection or HIV-related dementia is known
or suspected.
AND/OR

Benzodiazepine, repeat as necessary, to achieve containment, e.g.:

Lorazepam, IM, 1–4 mg.
OR
Clonazepam, IM, 0.5–2 mg.
OR
Diazepam, IV, 10 mg.
o Switch to oral route once containment is achieved.
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PSYCHIATRIC DISORDERS
Note:
CAUTION
Benzodiazepines, especially diazepam IV, can cause respiratory depression.
Monitor patients closely.
»
»
»
»
»
»
In the frail and elderly patient or where respiratory depression is a
xi
concern, reduce the dose by half.
LoE:III
The safest route of administration is oral followed by IM
with the IV route having the highest risk of respiratory depression and
arrest. Use the safest route wherever possible.
Monitor vital signs closely during and after administration.
Use haloperidol instead of benzodiazepines in patients with respiratory
insufficiency.
In the short-term, benzodiazepines can aggravate delirium.
To avoid inappropriate repeat dosing allow at least 15–30 minutes for
the medication to take effect. Repeated IM doses of benzodiazepines
may result in toxicity owing to accumulation.
15.3 BIPOLAR DISORDER
F31.9
DESCRIPTION
Bipolar disorder is a lifelong illness, which may have an episodic, variable
course. The presenting episode may be manic, hypomanic, or depressive. By
definition, a diagnosis of bipolar disorder requires either a current or previous
episode of mania or hypomania, and a past or current major depressive
episode.
An episode of mania is typically characterised by an elevated mood (e.g.
extreme happiness or irritability). This mood disturbance may be associated
with increased energy/goal-directed activity, talkativeness and flight of ideas,
a reduction in the need for sleep, and grandiosity and/or religiose delusions.
Even during periods of relative euthymia, i.e. without either clearly manic or
depressive features, patients may still experience impairments in
psychosocial functioning.
GENERAL MEASURES
Hospitalisation may be required during acute mania.
Psychotherapy, usually after the manic episode has been controlled with
medication.
Family therapy and psycho-education of patient and family to increase
adherence and knowledge of the condition.
In severe cases, psychiatrist directed electroconvulsive therapy may be required.
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MEDICINE TREATMENT
Manic episodes
Acute management
Manage as for any aggressively disruptive adult (see section 15.1:
Aggressive disruptive behaviour in adults).
LoE:IIxxxii
LoE:IIxxxiii
LoE:Ixxxiv
Maintenance therapy
Indicated once the patient is cooperative.
Lithium is the treatment of choice. The full therapeutic effect may require days
to weeks. Check renal and thyroid function before initiating lithium therapy.
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CAUTION
Therapeutic drug monitoring is essential when using lithium.
Clinical toxicity may occur even within the therapeutic range.
Concomitant use of many medicines e.g. ACE-inhibitors, NSAIDs and
diuretics may increase the risk of lithium toxicity.

Lithium, oral, 250 mg 12 hourly.
o Usual dose range: 200–500 mg/dose 12 hourly.
o May be given as a single total daily dose at night to enhance
adherence.
o Monitor trough (pre-dose) plasma levels after 5 days.
o Lithium has a narrow therapeutic window. The therapeutic range is
0.4–0.8 mmol/L for maintenance therapy, and 0.8–1.0 mmol/L in
mania.
o If levels are sub-therapeutic and the patient is adherent increase
the dose by 250 mg and repeat trough plasma levels after 5 days.
o Maintain therapeutic blood levels of lithium for as long as the patient is
on lithium. Monitor lithium levels and renal function at least monthly for
the first 3 months of therapy.
o Monitor lithium levels 6 monthly once stable levels have been
achieved, together with serum creatinine, sodium and potassium.
o Check TSH (for lithium-induced hypothyroidism) and serum calcium
(for lithium-induced hyperparathyroidism) before starting treatment and
annually thereafter.
o Monitor creatinine level, sodium and potassium 6 monthly.
xii
LoE:III
AND/OR
 Valproate, oral, 300 mg 12 hourly.
o Increase dose incrementally to a maximum dose of
LoE:III
20 mg/kg/day 12 hourly.
Acute bipolar depressive episodes
Can be difficult to manage, have a high suicide risk, and is best managed in
consultation with a psychiatrist.
Note:
» Do not use antidepressants as monotherapy in bipolar patients.
» Patients on atypical antipsychotics (e.g. risperidone, amisulpiride
olanzapine and clozapine) need regular monitoring for metabolic sideeffects:
- Weight, BMI and waist circumference.
- Serum glucose and lipids.
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LoE:Ixxxiv
LoE:Ixxxiv
LoE:Ixxxiv
REFERRAL
To psychiatric services:
» Mixed features or rapid cycling bipolar disorder.
» Depressive episodes in bipolar patients not responding to second line
treatment.
» Manic episodes not responding to treatment.
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15.4 DEPRESSIVE DISORDER, MAJOR
F32.9
DESCRIPTION
Major depression is characterised by a depressed mood (sadness)
accompanied by loss of interest and decreased experience of pleasure, and
social withdrawal. Irritability may also occur, especially amongst
adolescents. Reduction in sleep, appetite, energy, motivation, concentration
and memory may occur. The patient may report feelings of worthlessness
and hopelessness, and express thoughts of suicide. Symptoms are usually
present for at least two weeks and impact on the person’s ability to function
normally.
Exclude underlying medical conditions that may present with depression,
e.g. thyroid disease.
GENERAL MEASURES
Supportive psychotherapy.
Counseling of patient and family
Address social factors.
Electroconvulsive therapy is indicated under specific circumstances in
consultation with a specialist.
MEDICINE TREATMENT
Antidepressant therapy
Antidepressants take 4–6 weeks to achieve their maximum effect. There is
little evidence to support combination medicine treatment.
Tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors
(SSRIs) are of equal efficacy.
The choice of therapy is guided by co-morbid states, e.g. avoid TCAs in
patients with cardiac disease or a high risk of overdose or in the elderly.
Following remission continue pharmacotherapy for at least another 6 months.
Thereafter taper off slowly to avoid discontinuation symptoms. If there is a
recurrence, reinstitute the medicineat the same dose.
Patients with ≥ 3 episodes may require maintenance pharmacotherapy to be
reviewed every 2 years.
Adolescents with depression are at increased risk of suicidal ideation
when initiated on SSRIs.
Major depressive disorder
First line

Selective serotonin reuptake inhibitors, e.g.:

Fluoxetine, oral.
o Initial dose: 20 mg
o If there is no or partial response after 4–8 weeks, increase to 40
2015
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PSYCHIATRIC DISORDERS
mg, if well tolerated.
OR
Citalopram, oral.
o Initial dose: 20 mg
o If there is no or partial response after 4–8 weeks, increase to 40
mg, if well tolerated.
xiii
LoE:I
OR


Tricyclic antidepressants, e.g.:
Amitriptyline, oral, at bedtime.
o Dose range: 75 – 150 mg.
o Start with: 25 mg, increase by 25 mg/day at 3–4 day intervals.
xiv
LoE:III
Second line
If on an SSRI change to another SSRI (citalopram) or a TCA.
If on a TCA change to a SSRI.
If initially on fluoxetine, wait for 7 days after stopping fluoxetine before
starting the other SSRI.
REFERRAL
»
»
»
Inadequate response to treatment.
High suicide risk.
Psychotic features.
15.5
PERSISTENT DEPRESSIVE DISORDER
(DYSTHYMIC DISORDER)
F34.1
DESCRIPTION
This condition presents with a depressed mood present for most of the time
for at least two years and tends to be chronic. Symptomatically it is similar to
major depression but does not fulfill the diagnostic criteria. In addition, the
depressed mood is continuous rather than episodic. Always consider the
possibility of substance abuse.
GENERAL MEASURES
As for Major Depressive Disorder.
MEDICINE TREATMENT
As for Major Depressive Disorder.
REFERRAL
No response to treatment.
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15.6 GENERALISED ANXIETY DISORDER
F41.1
DESCRIPTION
Generalised anxiety disorder is characterised by excessive and
inappropriate worry/concern about a range of issues. The patient may report
disturbances in sleep, concentration, or mood. Physical symptoms such as
muscle tension or tremulousness may also be reported.
GENERAL MEASURES
Psychotherapy.
Most patients can be treated as outpatients, but some may need to be
admitted.
MEDICINE TREATMENT
Indicated where symptoms are interfering with normal functions of daily living.
Where there is concomitant drug/alcohol dependence or co-morbid major
depressive episode, an antidepressant may be more appropriate.
Acute management
For an acute episode or intense prolonged anxiety:

Benzodiazepines, e.g.:

Diazepam, oral, 2–5 mg as a single dose.
o Repeat if required up to 12 hourly.
o Duration of therapy: up to 2 weeks tapering off to zero within 6
weeks.
See the note regarding benzodiazepines in section 15.2: Confusional
states/delirium.
Maintenance therapy

SSRI, e.g.:

Citalopram, oral, 10–40 mg daily.
xv
OR
LoE:III
Fluoxetine, oral, 10–40 mg daily.
o Duration of therapy: variable, although the condition tends to be
chronic.
o Extended medicine treatment should be monitored by a specialist.
xvi
LoE:I
CAUTION
Prolonged treatment with benzodiazepines often leads to tolerance and
withdrawal symptoms if the medicine is discontinued abruptly.
Combination therapy with more than one benzodiazepine is not indicated .
REFERRAL
Ongoing symptoms despite treatment.
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15.7 OBSESSIVE-COMPULSIVE DISORDER
F42.9
DESCRIPTION
This condition is characterised by the presence of persistent intrusive
thoughts or concerns, and is usually associated with compulsions, which are
mental acts or behaviours related to the obsessions, e.g. excessive hand
washing. Obsessive thoughts and compulsions may interfere with daily
functioning. The features are usually distressing to the patient.
MEDICINE TREATMENT


Selective serotonin reuptake inhibitors, e.g.:
Fluoxetine, oral.
o Initial dose: 20 mg
o If there is no or partial response after 4–8 weeks, increase to 40
mg, if well tolerated.
xvii
LoE:III
OR
Citalopram, oral.
o Initial dose: 20 mg
o If there is no or partial response after 4–8 weeks, increase to 40
mg, if well tolerated.
xviii
LoE:III
REFERRAL
Inadequate response to treatment.
15.8 PANIC DISORDER
F41.0
DESCRIPTION
A panic attack is characterised by an acute onset of intense anxiety
accompanied by a sense of dread/impending threat, usually for no apparent
reason. The patient will experience significant fear and emotional discomfort,
typically peaking within 10 minutes and resolving within 30 minutes. There
will usually be accompanying physical symptoms such as rapid
pulse/palpitations, shortness of breath, dizziness and sweating.
Panic disorder is diagnosed if panic attacks recur, with intervening periods of
comparative freedom from anxiety between attacks.
GENERAL MEASURES
Psycho-education and reassurance.
Psychotherapy, e.g. cognitive-behaviour therapy.
Exclude an underlying medical condition, e.g. thyrotoxicosis.
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MEDICINE TREATMENT
Panic attack
Acute management
The initial aim is to control the panic symptoms and exclude an underlying
medical cause.

Benzodiazepines, repeated as necessary to control symptoms, e.g.:

Lorazepam, oral, 2 mg, immediately.
OR
Clonazepam, oral, 1 mg, immediately.
OR
Diazepam, oral, 5 mg, immediately.
OR
Midazolam, oral or buccal, 7.5 mg, immediately.
See the note regarding benzodiazepines in section 15.2: Confusional
states/delirium.
Panic disorder
xix

SSRI, e.g.:
LoE:III

Citalopram, oral, 10–40 mg daily.
OR
Fluoxetine, oral, 20–40 mg daily.
o Initiate at low dose and gradually titrate to therapeutic dosages
according to tolerability.
o SSRI’s onset of action in panic disorder is relatively slow, and at
least 8 weeks of adequate dose treatment is required before
efficacy can be assessed.
o Duration of SSRI therapy: variable, initially 6 months–1 year.
o Long term medicine treatment may be necessary.
o Relapses may occur when treatment is discontinued.
o Consider short term co-administration of a benzodiazepine, due to
the slow onset of action and the potential for increased anxiety
during the initial phase of treatment with antidepressants.
REFERRAL
Treatment resistant panic disorder or need for benzodiazepine treatment
beyond 6 weeks.
15.9 ACUTE STRESS DISORDER AND POST-TRAUMATIC
STRESS DISORDER
F43.0/F43.1
DESCRIPTION
Acute stress and post-traumatic stress disorder arise in response to stressful
events. The patient should have experienced the event as life threatening or
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PSYCHIATRIC DISORDERS
as a physical threat to themselves or others, at which time they felt fear and
helplessness.
A range of symptoms are associated with both of these conditions and
include:
» Re-experiencing of the event, e.g. flashbacks, dreams.
» Avoidance of situations associated with the event.
» Features of anxiety or increased arousal, e.g. hypervigilance,
heightened startle response and insomnia.
The conditions are symptomatically similar but differ with regard to the
duration and time of onset of symptoms. The symptoms of acute stress
disorder arise within 4 weeks of the event and last up to 4 weeks, whereas
the symptoms post-traumatic stress disorder last longer than 4 weeks, and
may arise more than 4 weeks after the traumatic incident.
GENERAL MEASURES
Reassurance and support of patient and family.
Psychotherapy, usually of a supportive/cognitive-behavioural nature.
Trauma debriefing is not routinely recommended.
MEDICINE TREATMENT
Acute stress disorder:
Benzodiazepines may be useful in the immediate period following the
traumatic event.
Prolonged use > 1 week may be detrimental to adaptation, leading to higher
rates of post-traumatic stress disorder.
For acute anxiety or agitation:

Clonazepam, oral 0.5–2 mg in divided doses.
xx
For sleep disturbance: See section 15.13: Insomnia.
LoE:III
Post-traumatic stress-disorder:

Selective serotonin reuptake inhibitors, e.g.:
xxi
LoE:III

Citalopram, oral, initial dose 20 mg daily.
OR
Fluoxetine, oral, initial dose 20 mg in the morning.
o A response to SSRI should be expected after 4–6 weeks.
o If there is no or partial response after 4–8 weeks, increase SSRI dose
to 40 mg, if well tolerated.
o An adequate trail of treatment is 8–12 weeks, before an alternative
treatment should be considered.
REFERRAL
»
»
Persistent symptoms.
Inadequate response to treatment.
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»
PSYCHIATRIC DISORDERS
Co-morbid conditions.
15.10 PSYCHOSIS, ACUTE
DESCRIPTION
Psychosis is characterised by loss of contact with reality. The patient may
experience perceptual disturbances, e.g. auditory hallucinations, and
delusions. There may be accompanying behavioural disturbances related to
both perceptual and thought disturbances. This presentation is characteristic
of psychotic disorders, such as schizophrenia. However, this presentation
may occur in other psychiatric conditions (e.g. bipolar mania, major
depression) or medical conditions (e.g. certain types of epilepsy). The
presentation may be acute or chronic. Patients generally have no insight into
their symptoms and may be resistant to intervention.
See section 15.3: Bipolar Disorder and section 15.11: Schizophrenia.
15.11 SCHIZOPHRENIA
F20-F20.9
DESCRIPTION
Schizophrenia is characterised by psychotic episodes, and is typically
accompanied by deterioration in social, general and occupational
functioning. Whilst the presentation may be acute, typically the illness has a
chronic course.
GENERAL MEASURES
Supportive psychotherapy and psycho-educational group therapy for
patients and family members.
MEDICINE TREATMENT
Psychotic episode
Acute management
For the agitated and acutely disturbed patient: see Section 15.1: Aggressive
disruptive behaviour in adults.
First episode:
 Haloperidol, oral.
o Initial dose: 1 mg daily, increasing to 5 mg daily.
OR
 Risperidone, oral.
o Initial dose: 2–4 mg daily.
o Assess efficacy after 4–6 weeks.
If a partial response is noted, optimise the dosage.
2015
xxii
LoE:III
xxiii
LoE:I
15.14
CHAPTER 15
PSYCHIATRIC DISORDERS
If no response is noted, switch treatment.
OR

Chlorpromazine, oral, 75–300 mg daily in divided doses.
OR
If adherence is a problem or patients’ preference:
 Depot antipsychotic, e.g.:
 Flupenthixol decanoate, IM, 20–40 mg every 4 weeks.
OR
Fluphenazine decanoate, IM, 12.5–50 mg every 4 weeks.
OR
Zuclopenthixol decanoate, IM, 200-600 mg every 4 weeks.
xxiv
LoE:III
xxv
LoE:III
xxvi
LoE:III
If extrapyramidal side-effects occur with the lowest effective
dose of antipsychotic medication:
Switch from haloperidol or chlorpromazine to risperidone.
If this is not tolerated or if the extrapyramidal side-effects persist, add:
 Anticholinergic agent, e.g.:
 Orphenadrine, oral, 50–150 mg daily according to individual response
o Usual dose: 50 mg 12 hourly.
o Maximum dose: 150 mg daily.
o Use with caution in the elderly as it may cause confusion and urinary
retention.
Note: Anticholinergic medicines (e.g. orphenadrine) should not be added
prophylactically to antipsychotics to prevent extrapyramidal side effects.
If akathisia (a subjective unpleasant state of inner restlessness where there
is a strong desire or compulsion to move) develops:

Propranolol, oral,
xxvii
o
Start at 20mg daily and titrate as needed up to 80
LoE:II
mg 8 hourly.
o
Monitor pulse and blood pressure.
Maintenance therapy
» Specialist initiated.
» Psychiatrist to review patients every 6 months.
Treatment resistant cases, not responding to risperidone and/or haloperidol
must be referred to tertiary level care. Psychiatrists may initiate other second
generation antipsychotics; and in treatment resistant cases clozapine.
» Atypical antipsychotics need regular monitoring for metabolic side-effects.
- Weight, BMI and waist circumference
- Serum glucose and lipids
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»
PSYCHIATRIC DISORDERS
Clozapine needs frequent WCC monitoring: Weekly for the first 18 weeks,
then every 2 weeks for the next 6 months, then monthly.
9
- If neutrophils < 1.5 x10 /L, stop the medication.
9
- If neutrophils < 0.5x10 /L, refer to specialist medical care.
REFERRAL
»
»
»
»
Psychotic patients with uncertain diagnosis.
Patients who relapse and refuse treatment or become aggressive or
suicidal, refer to the mental health care act in terms of involuntary
treatment.
Patients with complications due to medication.
Poor response to therapy.
15.12 WITHDRAWAL FROM SUBSTANCES OF ABUSE
15.12.1 ALCOHOL
F10.4
GENERAL MEASURES
The following patients should be admitted for detoxification:
» past history of convulsions
» past history of psychosis
» suicidal ideation
» significant medical co-morbidity such as heart failure and liver disease
» inadequate support at home
» history of withdrawal delirium
» > 60 years of age
» pregnancy
» cognitive impairment
» previous failed community detoxification attempts
MEDICINE TREATMENT
Alcohol detoxification may be managed on an outpatient basis in most
patients.
 Thiamine, oral, 300 mg daily for 14 days.
AND
 Diazepam, oral, 10 mg immediately.
o Then 5 mg 6 hourly for 3 days.
o Then 5 mg 12 hourly for 2 days.
o Then 5 mg daily for 2 days.
o Then stop.
o Higher doses may be needed in individual patients.
2015
xxviii
LoE:III
15.16
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15.12.2 ALCOHOL WITHDRAWAL DELIRIUM (DELIRIUM
TREMENS)
F10.4
DESCRIPTION
Delirium typically occurs 2–3 days following cessation of prolonged alcohol
intake, reaching a peak at around 5 days. However, some withdrawal
symptoms, such as tremor, may start within 12 hours.
Typical clinical features include:
» visual hallucinations,
» delusions,
» disorientation, fluctuating level of consciousness,
» agitation,
» tonic-clonic seizures – these do not generally need long term
anticonvulsant therapy,
» tachycardia, and
» hypertension.
It is important to consider alternative diagnoses, especially true in cases with
an atypical presentation.
Similar symptoms may occur following withdrawal from other sedativehypnotic agents.
Mortality varies from 1–5%.
GENERAL MEASURES
See section 15.2: Confusional states/Delirium for management.
Cardiac monitoring and oximetry should be used when administering large
doses of benzodiazepines.
Assess for infections and other co-morbid conditions.
Ensure adequate hydration. Overhydration is a common error made in this
setting.
Correct abnormalities of electrolytes.
Nutritional support.
Consider referring appropriate patients to a rehabilitation programme after
recovery from delirium tremens.
MEDICINE TREATMENT
Administer medicine doses according to severity of symptoms. These
patients may require high doses of benzodiazepines because of hepatic
enzyme induction.


Benzodiazepines, e.g.:
Diazepam, slow IV, 10 mg (Not IM).
o Repeat dose after 5–10 minutes if required.
o If this dose is not sufficient, use 10 mg every 5–10 minutes for
another 1–2 doses.
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o
PSYCHIATRIC DISORDERS
If patient is not yet sedated, continue with doses of 20 mg until this
occurs. Usual initial dose is 10–20 mg, but up to 60 mg is
occasionally required.
OR
Where intravenous access is not possible:

Clonazepam, IM, 2 mg as a single dose.
o If no response, repeat dose after 60 minutes until patient is sedated.
o Repeat dose regularly to maintain mild sedation.
LoE:III
OR
Lorazepam, IM, 1–4 mg every 30–60 minutes until patient is sedated.
o Repeat dose regularly to maintain mild sedation.
LoE:III
Once patient is sedated, i.e. light somnolence, maintain mild sedation with:

Diazepam, oral, 5–20 mg.
o Repeat dose regularly to maintain mild sedation.
LoE:III
CAUTION
Benzodiazepines, especially diazepam IV, can cause respiratory depression.
Monitor patients closely as benzodiazepines can exacerbate an abnormal
mental state or mask important neurological signs of deterioration.
See the note regarding benzodiazepines in section 15.2: Confusional
states/delirium.
Neuroleptic medicines, e.g. haloperidol, are associated with a reduced
seizure threshold. Consider only for severe agitation and restlessness
persisting after adequate doses of benzodiazepines.

Haloperidol, IV/IM, 0.5–5 mg.
o Repeat after 4–8 hours as required to a maximum of 20 mg daily.
Once patient has responded and is able to take oral medication:

Haloperidol, oral, 0.5–5 mg 4–8 hourly.
When administering glucose-containing fluids:

Thiamine, oral/IM, 300 mg daily.
15.12.3 OPIATE WITHDRAWAL, E.G. HEROIN
F11.2
DESCRIPTION
Withdrawal is generally poorly tolerated, but not dangerous, except in very
frail debilitated patients or during pregnancy, with an increased risk of
miscarriage in the first trimester and of preterm delivery in the third trimester.
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Signs and symptoms of opiate intoxication:
» Pinpoint pupils
» Drowsiness
» Clammy skin
» Euphoria
» Respiratory depression
» Hallucinations
Signs and symptoms of opiate withdrawal:
» Nausea
» Myalgia
» Gooseflesh
» Diarrhoea
» Rhinorrhoea and lacrimation
MEDICINE TREATMENT
Mild withdrawal
May be managed on an outpatient basis.
Symptomatic treatment

Diazepam, oral, 5–20 mg/day in divided doses.
o Taper off over 5–7 days.
For stomach cramps:

Hyoscine butylbromide, oral, 20 mg 8 hourly as required.
For headaches:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
LoE:III
o Maximum dose: 4 g in 24 hours.
For muscle pains:

Ibuprofen, oral 400 mg 8 hourly, with meals, as required.
For diarrhoea:

Loperamide, oral, 4 mg immediately.
o Then 2 mg after each loose stool.
o Maximum dose: 16 mg in 24 hours.
LoE:III
Moderate to severe withdrawal
Hospitalise patient.
Substitution treatment
Day 1: Only if clinical signs of withdrawal are present.
xxix
LoE:III

Methadone, oral, 5–10 mg.
o If symptoms are still present after 2-4 hour, give
another 5–10 mg.
o The initial dose to suppress withdrawal symptoms may be repeated
after 12 hours.
o The total 24 hour dose should rarely be more than 30 mg. Consult a
person experienced in opioid withdrawal when prescribing > 30
mg/day.
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PSYCHIATRIC DISORDERS
Day 2:

Methadone, oral.
o Repeat total dose of day 1 as a single or 2 divided doses.
o Monitor for on-going sign and symptoms of withdrawal.
o If the sing and symptoms of withdrawal are still present on day 2,
top-up doses of 5 mg may be given at 2–4 hourly intervals with a
total daily dose of 30 mg.
Day 3 onwards:

Methadone, oral.
o Decrease by 5 mg/day to a total of 10 mg. Thereafter, reduce by 2
mg/day.
o The withdrawal regimen may be shortened if the patient’s
withdrawal symptoms allow it.
o Repeat total dose of day 2 if top-ups were needed and begin
reductions on day 4.
If methadone is unavailable:

Tramadol, oral, 200 mg 12 hourly for 14 days may attenuate withdrawal
symptoms.
xxx
LoE:II
15.12.4 STIMULANT WITHDRAWAL, INCLUDING
COCAINE AND METHAMPHETAMINES
F14.2
GENERAL MEASURES
These patients usually do not require admission.
Beware of depression and assess suicide risk.
Assess and monitor for psychosis.
MEDICINE TREATMENT
No substitute medication available for detoxification.
For severe anxiety, irritability and insomnia:

Benzodiazepines, short-term, e.g.:

Diazepam, oral, 5–10 mg 8 hourly for 5–7 days.
15.12.5 METHAQUALONE WITHDRAWAL
F19.4/F19.9
Withdrawal can be dangerous and may lead to seizures or delirium.
If withdrawal is symptomatic:

Diazepam, oral, 5 mg 8 hourly.
o Reduce over 3–5 days depending on clinical response.
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15.12.6 CANNABIS WITHDRAWAL
F12.2
Withdrawal is rarely dangerous and poorly tolerated.
Assess for other accompanying psychiatric disorders e.g. mood or psychosis.
15.12.7 BENZODIAZEPINE WITHDRAWAL
F13.2
GENERAL MEASURES
The therapeutic relationship between client and doctor is extremely important
in initiating dose reduction. Take time to explain concepts like tolerance and
withdrawal to the patient and then convince them that stopping the
benzodiazepine is the best thing to do. Encourage the patient not to seek
medication from other doctors. Negotiate each reduction with the patient.
Avoid abrupt withdrawal of benzodiazepines.
Withdrawal from benzodiazepines takes time.
The patient will require regular monitoring and motivation.
MEDICINE TREATMENT
Replace short-acting benzodiazepine with an equivalent diazepam (long
acting benzodiazepine) dose.
Patients may present with medicines that are unavailable in the public
sector. Approximate equivalent doses to diazepam 5 mg are:
» chlordiazepoxide 15 mg
» lorazepam 1 mg
» alprazolam 0.5 mg
» bromazepam 1.5 mg
» flunitrazepam 0.5 mg
» nitrazepam 5 mg
» oxazepam 15 mg
» temazepam 10 mg
» zopiclone 7.5 mg
» zolpidem 10 mg
Note: Medicines have only been included for comparison of estimated
equivalent doses.
Patients are not always truthful about the amount of benzodiazepine used.
Even if the equivalent dose of diazepam is higher than 30 mg/day, start on
30 mg/day in divided doses and adjust upwards or downwards, depending
on clinical response.
Decrease the dose of diazepam every 2 weeks by 2.5 mg. If symptoms
reappear increase the dose a little and reduce dose over longer intervals.
Withdrawal
symptoms
include
anxiety,
nervousness,
irritability,
depersonalisation, delirium and seizures, increased sweating, sound
`
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PSYCHIATRIC DISORDERS
sensitivity, nausea, difficulty concentrating, myoclonus, tremor, weakness
and fatigue.
REFERRAL
All patients treated for substance withdrawal should be referred to Social
Services for rehabilitation and aftercare.
15.13 INSOMNIA
G47.0/G47.9
DESCRIPTION
Insomnia may be an independent disorder, or associated with co-morbid
conditions. Insomnia may persist despite successful treatment of the comorbidity, and may necessitate separate treatment.
Patients presenting with insomnia may complain of difficulty falling asleep,
frequent waking during the night, early-morning wakening and daytime
sleepiness.
GENERAL MEASURES
Treat the medical condition, psychiatric illness, substance use disorder or
sleep disorder that may be precipitating or exacerbating the insomnia, if
present.
All patients should receive basic behavioural counselling about sleep hygiene
and stimulus control as first step of treatment.
Cognitive behavioural therapy is the treatment of choice.
MEDICINE TREATMENT
If medication is needed:
» Use the lowest effective dose.
» Use intermittent dosing if possible (alternate night or less).
Sleep hygiene and stimulus control:
» Maintain a regular sleep cycle (same time wake up in the morning,
including week-ends).
» Stimulus control:
- Keeping the room quiet, dark and at a comfortable temperature.
- Using the bed and bedroom only for sleeping (and sex).
» Limit intake of caffeine, nicotine and alcohol, especially before bedtime.
» Eating a light snack before bedtime, but not a large meal late at night.
» Sleep restriction: avoiding daytime naps.
» Increasing daily exercise (not late in the evening).
» Using anxiety management or relaxation techniques.
» Go to bed only when tired. Sleep as much as needed to feel refresh, not
longer.
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»
PSYCHIATRIC DISORDERS
If unable to sleep for more than 15–20 minutes, get out of bed and
engage in a non-stimulating activity until tired (e.g. listen to soft music,
read).
If medication is needed to treat the insomnia:

Short-acting benzodiazepines, e.g.:

Oxazepam, oral 15–30 mg at night.
Short-term use of benzodiazepines of 14 days is recommended as long-term
use is often associated with dependence.
xxxi
LoE:I
REFERRAL
Patients with chronic insomnia.
15.14 DISCONTINUATION SYMPTOMS OF SEROTONIN
REUPTAKE INHIBITORS
Discontinuation symptoms are experienced due to receptor adaptation or
receptor rebound after stopping of antidepressants. It can be avoided or
reduced by slowly tapering the drug over at least 4 weeks.
Symptoms include flu-like symptoms, ‘shock-like” sensations, dizziness
exacerbated by movement, insomnia, vivid dreaming and irritability,
problems with concentration and memory or movement disorders.
It is managed by reintroduction of the SSRI and slower tapering the dose.
Note: Fluoxetine seldom causes discontinuation symptoms because of its
long half life.
References:
i
Benzodiazepines:Gillies D, Sampson S, Beck A, Rathbone J. Benzodiazepines for psychosis-induced
aggression or agitation. Cochrane Database Syst Rev. 2013 Apr 30;4:CD003079.
http://www.ncbi.nlm.nih.gov/pubmed/23633309
ii
Lorazepam, oral: SAMF, 2014.
iii
Clonazepam, oral: SAMF, 2014.
iv
Diazepam, oral: PHC STGs and EML, 2014. http://www.health.gov.za/
Diazepam, oral: SAMF, 2014.
v
Midazolam, buccal: Taylor D, Okocha C, Paton C, Smith S, Connolly A. Buccal midazolam for agitation on
psychiatric intensive care wards.Int J Psychiatry ClinPract.2008;12(4):309-11.
http://www.ncbi.nlm.nih.gov/pubmed/24937720
Midazolam, bucal: PHC STGs and EML, 2014. http://www.health.gov.za/
Midazolam, oral: SAMF, 2014.
vi
Benzodiazepines, parenteral:Gillies D, Sampson S, Beck A, Rathbone J. Benzodiazepines for psychosisinduced aggression or agitation. Cochrane Database Syst Rev. 2013 Apr 30;4:CD003079.
http://www.ncbi.nlm.nih.gov/pubmed/23633309
Benzodiazepines, parenteral: PHC STGs and EML, 2014. http://www.health.gov.za/
vii
Lorazepam, IM: Alexander J, Tharyan P, Adams C, John T, Mol C, Philip J. Rapid tranquillisation of violent or
agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v.
haloperidol plus promethazine. Br J Psychiatry. 2004 Jul;185:63-9. http://www.ncbi.nlm.nih.gov/pubmed/15231557
viii
Promethazine, IM: PHC STG and EML, 2014. http://www.health.gov.za/
Promethazine, IM: Huf G, Coutinho ES, Adams CE; TREC Collaborative Group. Rapid tranquillisation in psychiatric
emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular
haloperidol plus promethazine. BMJ. 2007 Oct 27;335(7625):869. http://www.ncbi.nlm.nih.gov/pubmed/17954515
ix
Chlopromazine, IM: PHC STGs and EML, 2014. http://www.health.gov.za/
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x
Zuclopenthixol acetate, IM: PHC STGs and EML, 2014. http://www.health.gov.za/
Benzodiazepines/ Haloperidol: SAMF, 2014.
Amitryptiline: SAMF, 2014.
xiii
Selective serotonin reuptake inhibitors: NICE Guidelines: The treatment and management of depression in
adults. NICE clinical guideline 90. [Online][Accessed 24March2015] Available at: www.guidance.nice.org.uk/cg90
Selective serotonin reuptake inhibitors: Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G,
Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A. Evidence-based guidelines for treating
depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology
guidelines. J Psychopharmacol. 2008 Jun;22(4):343-96. http://www.ncbi.nlm.nih.gov/pubmed/18413657
Selective serotonin reuptake inhibitors: Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden
D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ,
Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment
steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17.
http://www.ncbi.nlm.nih.gov/pubmed/17074942
xiv
Amitryptiline: SAMF, 2014.
xv
Citalopram: NICE. NICE clicnial guideline CG113: Generalised anxiety disorder and panic disorder (with or
without agoraphobia) in adults: Management in primary, secondary and community care, January 2011.
http://www.nice.org.uk/guidance/cg113
Citalopram: PHC STGs and EML, 2014. http://www.health.gov.za/
xvi
Fluoxetine: Zou C, Ding X, Flaherty JH, Dong B. Clinical efficacy and safety of fluoxetine in generalized anxiety
disorder in Chinese patients. Neuropsychiatr Dis Treat. 2013;9:1661-70. http://www.ncbi.nlm.nih.gov/pubmed
/24204151
Fluoxetine: SAMF, 2014.
xvii
Fluoxetine: SAMF, 2014.
xviii
Citalopram: SAMF, 2014.
xix
Selective serotonin reuptake inhibitors: Batelaan NM, Van Balkom AJ, Stein DJ. Evidence-based
pharmacotherapy of panic disorder: an update. Int J Neuropsychopharmacol. 2012 Apr;15(3):403-15.
http://www.ncbi.nlm.nih.gov/pubmed /21733234
xx
Clonazepam – acute stress disorder: Mellman TA, Byers PM, Augenstein JS. Pilot evaluation of hypnotic
medication during acute traumatic stress response. J Trauma Stress. 1998 Jul;11(3):563-9.
Clonazepam – acute stress disorder: Tol WA, Barbui C, van Ommeren M. Management of acute stress, PTSD,
and bereavement: WHO recommendations. JAMA. 2013 Aug 7;310(5):477-8.
xxi
Selective serotonin reuptake inhibitors – post-traumatic stress disorder: Mellman TA, Byers PM, Augenstein JS.
Pilot evaluation of hypnotic medication during acute traumatic stress response. J Trauma Stress. 1998
Jul;11(3):563-9.
Selective serotonin reuptake inhibitors – post-traumatic stress disorder: Tol WA, Barbui C, van Ommeren M.
Management of acute stress, PTSD, and bereavement: WHO recommendations. JAMA. 2013 Aug 7;310(5):477-8.
xxii
Haloperidol, oral: PHC STGs and EML, 2014. http://www.health.gov.za/
xxiii
Risoeridone, oral:Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus firstgeneration antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-41.
http://www.ncbi.nlm.nih.gov/pubmed/19058842
Risperidone, oral: Crespo-Facorro B, Pérez-Iglesias R, Mata I, Ramirez-Bonilla M, Martínez-Garcia O, PardoGarcia G, Caseiro O, Pelayo-Terán JM, Vázquez-Barquero JL. Effectiveness of haloperidol, risperidone and
olanzapine in the treatment of first-episode non-affective psychosis: results of a randomized, flexible-dose, openlabel 1-year follow-up comparison. J Psychopharmacol.2011 Jun;25(6):744-54.
http://www.ncbi.nlm.nih.gov/pubmed/21292922
Risperidone, oral: PHC STGs and EML, 2014. http://www.health.gov.za/
xxiv
Flupenthixol decanoate, IM: SAMF, 2014.
xxv
Fluphenazine decanoate, IM: SAMF, 2014.
xxvi
Zuclopenthixol decanoate, IM: SAMF, 2014.
xxvii
Propanolol, oral: Poyurovsky M, Pashinian A, Weizman R, Fuchs C, Weizman A. Low-dose mirtazapine: a new
option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranololcontrolled trial. Biol Psychiatry 2006; 59: 1071– 7. http://www.ncbi.nlm.nih.gov/pubmed /16497273
xxviii
Thiamine, oral: Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and
treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev. 2013 Jul
1;7:CD004033. http://www.ncbi.nlm.nih.gov/pubmed/23818100
Thiamine, oral: PHC STGs and EML, 2014. http://www.health.gov.za/
Thiamine: Lingford-Hughes AR, Welch S, Peters L, Nutt DJ; British Association for Psychopharmacology,
Expert Reviewers Group. BAP updated guidelines: evidence-based guidelines for the pharmacological
management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J
Psychopharmacol. 2012 Jul;26(7):899- 952. http://www.ncbi.nlm.nih.gov/pubmed/22628390
xxix
Methadone, oral: National Department of Health. National Policy guidelines on detoxification of psychoactive
substances.http://www.health.gov.za/
xxx
Tramadol, oral: Chattopadhyay S, Singh OP, Bhattacharyya A, Sen S, Roy P, Debnath S. Tramadol versus
clonidine in management of heroin withdrawl. Asian J Psychiatr. 2010 Dec;3(4):237-9.
http://www.ncbi.nlm.nih.gov/pubmed/23050896
xi
xii
2015
15.24
CHAPTER 15
PSYCHIATRIC DISORDERS
xxx
Lofwall MR, Babalonis S, Nuzzo PA, Siegel A, Campbell C, Walsh SL. Efficacy of extended-release tramadol for
treatment of prescription opioid withdrawal: a two-phase randomized controlled trial. Drug Alcohol Depend. 2013
Nov 1;133(1):188-97. http://www.ncbi.nlm.nih.gov/pubmed/23755929
xxx
Lofwall MR, Walsh SL, Bigelow GE, Strain EC. Modest opioid withdrawal suppression efficacy of oral tramadol
in humans. Psychopharmacology (Berl). 2007 Oct;194(3):381-93. http://www.ncbi.nlm.nih.gov/pubmed/17605004
xxxi
Oxazepam: Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M. The
efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med.
2007 Sep;22(9):1335-50. http://www.ncbi.nlm.nih.gov/pubmed/17619935
xxxii
Lorazepam, oral/IM: Bradwejn J, Shriqui C, Koszycki D, Meterissian G. Double-blind comparison of the effects
of clonazepam and lorazepam in acute mania. J Clin Psychopharmacol. 1990 Dec;10(6):403-8.
http://www.ncbi.nlm.nih.gov/pubmed/2126794
xxxiii
Clonazepam, oral/IM: Curtin F, Schulz P. Clonazepam and lorazepam in acute mania: a Bayesian metaanalysis. J Affect Disord. 2004 Mar;78(3):201-8. http://www.ncbi.nlm.nih.gov/pubmed/15013244
xxxiv
Risperidone, oral: Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM,
Goodwin GM, Geddes JR. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multipletreatments meta-analysis. Lancet. 2011Oct 8;378(9799):1306-15. http://www.ncbi.nlm.nih.gov/pubmed/21851976
xxxv
Fluoxetine-olanzapine: Selle V, Schalkwijk S, Vázquez GH, Baldessarini RJ. Treatments for acute bipolar
depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.
Pharmacopsychiatry. 2014 Mar;47(2):43-52. http://www.ncbi.nlm.nih.gov/pubmed /24549862
Fluoxetine-olanzapine: Ketter TA, Miller S, Dell'Osso B, Calabrese JR, Frye MA, Citrome L. Balancing benefits
and harms of treatments for acute bipolar depression. J Affect Disord. 2014 Dec;169 Suppl 1:S24-33.
http://www.ncbi.nlm.nih.gov/pubmed /25533911
Fluoxetine-olanzapine: National Department of Health: Affordable Medicines, EDP-Adult Hospital level.
Medicine Review: Olanzapine-fluoxetine for depressive episodes in bipolar disorder, March 2015.
http://www.health.gov.za/
2015
15.25
CHAPTER 16
RESPIRATORY SYSTEM
16.1 ASTHMA, ACUTE
J45
GENERAL MEASURES
Ensure adequate hydration.
In patients presenting with asthma for the first time, the diagnosis of
pulmonary oedema due to left ventricular heart failure should be considered.
Patients with severe asthma (characterised by one or more of: unable to
complete sentences in one breath, altered mental status, paradoxical chest
movement, absence of wheezes, PEF < 50% of predicted/personal best see PEF charts on pg lxxvi) should ideally be closely monitored in a High
Care or an Intensive Care Unit.
MEDICINE TREATMENT
If hypoxic:

Oxygen.
Continuous nebulisation is preferable to intermittent nebulisation with ß2st
agonists for the 1 hour of therapy.

Salbutamol 5 mg (1 mL 0.5% respiratory solution with 4 mL sodium
i
chloride 0.9%).
LoE: I
o
Nebulise continuously (refill the nebuliser reservoir every 20
minutes) at a flow rate of 6–8 L/minute until PEF > 60% of
predicted/personal best.
o If response to nebulised salbutamol is poor, add ipratropium
st
bromide 0.5 mg with the 1 refill of the nebuliser reservoir.
ii
LoE: II
o Once a patient reaches 60% of their predicted/personal best PEF,
repeat salbutamol 5 mg or fenoterol 1.25–2.5 mg 4 hourly.
Note: Fenoterol should not be used for continuous nebulisation, as
a maximum safe dose in this setting has not been established.
iii
LoE:III
Continue nebulisations until PEF returns to 80% of predicted/ personal best,
at which point the patient can be converted to:

Salbutamol MDI, 2 puffs (200 mcg) as required.
AND

Prednisone, oral, 40 mg immediately (within 1 hour of presentation).
Follow with:

Prednisone, oral, 40 mg daily for 7 days.
iv
LoE:III
2015
16.1
CHAPTER 16
RESPIRATORY SYSTEM
OR
In patients who cannot use oral therapy or are vomiting:

Hydrocortisone, IV, 100 mg 6 hourly.
Once oral medication can be taken, switch to:

Prednisone, oral, 40 mg daily for 7 days
v
LoE:II
Monitor response with PEF and clinical signs. Patients who fail to respond
within 1 hour (symptomatic improvement and PEF > 60% of
predicted/personal best):
» Exclude upper airway obstruction/stridor, pneumothorax, and
anaphylaxis.
» Discuss management with a specialist.
» Intubation and ventilator support may be required.
» If referral to another facility is required the patient needs to be stabilised
prior to transfer and transported by the appropriate level of transport discuss with the referral centre.
In patients with a poor response:
ADD

Magnesium sulphate, IV, 2 g in 100 mL sodium chloride 0.9%, as a
vi
single dose, administered over 20 minutes.
LoE: I
Intravenous magnesium, single dose, has been shown to reduce the rate of
hospitalisation.
There is good evidence to recommend against the use of intravenous
aminophylline in acute asthma as its use together with high-dose nebulised
ß2-agonists does not result in significant additional bronchodilation and leads
to a significant increase in toxicity (vomiting and dysrhythmias).
vii
LoE: I
Intercurrent bacterial infections
Bacterial infections are seldom present in acute exacerbations of asthma
and yellow sputum is usually related to presence of eosinophils. Antibiotics
do not play a role in the management of asthma unless there is air space
consolidation on CXR. See section 16.6: Pneumonia, community acquired.
16.2 ASTHMA, CHRONIC PERSISTENT
J45
DESCRIPTION
Asthma must be distinguished from chronic obstructive pulmonary disease,
which is often mistaken for asthma. The history is a reliable diagnostic
guideline and may be of value in assessing treatment response.
2015
16.2
CHAPTER 16
Asthma
» Young age onset, usually < 20 years.
» History of hay fever, eczema and/or
allergies.
» Family history of asthma.
» Symptoms are intermittent with periods
of normal breathing in between.
» Symptoms are usually worse at night
or in the early hours of the morning,
during an upper respiratory tract
infection, when the weather changes
or when upset.
» Increase >15% in PEF 10 minutes
after receiving a ß2-agonist.
RESPIRATORY SYSTEM
COPD
» Older age onset, usually > 40 years.
» Symptoms slowly worsen over a
long period of time.
» Long history of daily/frequent cough,
before the onset of shortness of
breath.
» Symptoms are persistent and not only
at night or during the early morning.
» History of heavy smoking (> 20
cigarettes/day for ≥ 15 years), heavy
cannabis use or previous TB.
» Little improvement in PEF with ß2agonist.
GENERAL MEASURES
Patient education: including advice on smoking cessation.
Decrease exposure to triggers, e.g. house dust mite, pollens, grasses, pets,
smoke, fumes, etc.
MEDICINE TREATMENT
Concomitant use of preparations of the same therapeutic class is hazardous
and must be avoided.
Nocturnal symptoms of cough and wheeze, or the need for bronchodilators >
twice a week, or PEF < 80% of the patient’s best value, indicates poor asthma
control.
Patients with poorly controlled asthma need to step up their maintenance
therapy as described below.
The Asthma Control Test®, a validated measure of clinical asthma control, can
be completed by the patient (after initial instruction) at each visit to the clinic
prior to consultation. A value of ≥19 suggests adequate asthma control (See
page lxxviii).
A patient with poorly controlled asthma should be assessed for the following
and identified problems addressed prior to stepping up therapy:
1)
2)
3)
4)
5)
6)
2015
Correct inhaler technique should be demonstrated and checked
regularly, as many asthmatic patients do not use their inhalers correctly.
Adherence to medication, especially the inhaled corticosteroid.
Exposure to triggers of bronchospasm.
Use of medications that may aggravate asthma e.g. NSAIDS.
Other medical conditions such as cardiac disease.
Treat allergic rhinitis (see section 17.2: Rhinitis, allergic, persistent) and
GORD (see section 1.1.3: Gastro-oesophageal reflux disease (GORD), if
present.
16.3
CHAPTER 16
RESPIRATORY SYSTEM
Maintenance therapy
Inhaled corticosteroids (ICS) are the mainstay of treatment in chronic asthma:

ICS, e.g.:

Beclometasone, inhaled, 200 mcg 12 hourly starting dose.
o Control not optimal after 1 month: Increase dose to 400 mcg 12 hourly.
o Well and stable after 6 months: reduce dose by 200 mcg per day
every month, to determine the minimum dose to maintain control or
until a dose of 200 mcg, daily is achieved.
o Dose adjustments may be required at change of seasons.
viii
LoE: I
AND
As reliever/rescue therapy:

Short acting ß2-agonists, e.g.:

Salbutamol, MDI, 200 mcg, 6 hourly as necessary.
If insufficient response to high dose ICS (800 mcg beclomethasone daily)
and salbutamol, replace beclomethasone with:

Long-acting β2-agonist/corticosteroid combination inhaler, e.g.:

Salmeterol/fluticasone 50/250, one puff 12 hourly.
ix
AND
LoE: I
As reliever/rescue therapy:

Short acting ß2-agonists, e.g.:

Salbutamol, MDI, 200 mcg, 6 hourly as necessary.
Failure of above therapy:

While awaiting appointment with specialist.
ADD

Prednisone, oral 10 mg daily. Prednisone should not be used as
maintenance therapy but only as a bridging step while awaiting review
by a specialist.
LoE: III
For short-term exacerbations in patients not responding to the above, while
awaiting review with a specialist:
LoE: III

Prednisone, oral, 40 mg daily for 10 days.
PATIENT AND CAREGIVER EDUCATION ON INHALER AND SPACER
TECHNIQUES:
Spacer devices
Patients who are unable to use inhalers correctly after adequate counselling
may benefit from the use of a spacer.
Inhalation therapy without a spacer in adults:
1. Remove the cap from the mouthpiece.
2. Shake the inhaler well.
3. While standing or sitting upright, breathe out as much air as possible.
4. Place the mouth piece of the inhaler between the lips and gently close
the lips around it.
2015
16.4
CHAPTER 16
RESPIRATORY SYSTEM
5. While beginning to inhale, press down the canister of the metered dose
inhaler once to release one puff while breathing in as deeply as possible.
6. Hold the breath for 5–10 seconds, if possible.
7. Breathe out slowly and rest for a few breaths (30–60 seconds).
8. Repeat steps 2–6 for each puff prescribed.
9. Rinse mouth with water after inhalation of corticosteroids.
Inhalation therapy with a spacer in adults:
1. Remove the caps from the inhaler and the spacer.
2. Shake the inhaler well.
3. Insert the mouthpiece of the metered dose inhaler into the back of the
spacer.
4. Insert the mouthpiece of the spacer into the mouth and close the lips
around the mouthpiece. Avoid covering any small exhalation holes.
5. Press down the canister of the metered dose inhaler once to release one
puff into the spacer.
6. Immediately take 3–4 slow deep breaths.
7. Repeat steps 4–6 for each puff prescribed, waiting at least 30 seconds
between puffs.
8. Rinse mouth with water after inhalation of corticosteroids.
16.3 BRONCHIECTASIS
J47
GENERAL MEASURES
Patient education.
Advice on early self-referral for suspected acute infections.
Physiotherapy:
» Regular postural drainage is the mainstay of therapy and must be
emphasised and demonstrated to the patients.
» Regular home physiotherapy, including cough and chest drainage
techniques, and must be emphasised repetitively.
MEDICINE TREATMENT
Antimicrobial therapy
Antibiotic therapy in patients with bronchiectasis should only be used when
sputum becomes more purulent or sputum volume is greater volume than
usual. Antibiotic choices should be guided by sputum microscopy, culture
and sensitivity.
Treatment may need to be prolonged for two weeks, depending on the
extent of the bronchiectasis and the organisms suspected.
In patients otherwise stable and before culture results:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 10 days, or
x
longer depending on the response.
LoE:III
2015
16.5
CHAPTER 16
RESPIRATORY SYSTEM
Severe penicillin allergy:

Moxifloxacin, oral, 400 mg daily for at least 10 days, or longer
depending on the response.
More severely ill patients may require hospitalisation and initiation of
parenteral antibiotic therapy.
Sputum microscopy, culture and sensitivity determination are indicated in all
cases.

Ceftriaxone 2 g, IV, daily, until patient apyrexial for 24 hours.
xi
Follow with:
LoE:I

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
xii
LoE:III
If pseudomonas infection is suspected (confirm on culture):
ADD

Ciprofloxacin, oral, 750 mg 12 hourly for 7 days.
Caution
Irrational use of quinolones contributes to the emergence of XDR-TB and
potential masking of active TB.
xiii
LoE:II
Severe penicillin allergy:

Moxifloxacin, oral, 400 mg daily.
If penicillin allergic and unable to tolerate oral therapy:
Management of these patients should be discussed with a specialist for
possible referral and alternative parenteral therapy:

Moxifloxacin, IV, 400 mg daily infused over 60 minutes.
xiv
LoE:III
Switch to oral treatment once able to take orally:

Moxifloxacin, oral, 400 mg daily.
Subsequent antibiotic therapy should be based on results of sputum
investigations. A sputum smear for Acid Fast Bacilli (AFB), followed by
culture if positive, is recommended in patients with a poor response to
antibiotics as patients with bronchiectasis are at increased risk for infection
with Non-tuberculosis Mycobacteria which will not be detected by Xpert
MTB/RIF® PCR assay.
Inhaled bronchodilators
Bronchodilators may be used as for COPD, if airflow obstruction is present.
There is no indication for inhaled corticosteroids.
Any asthmatic component (i.e. reversible obstruction should be treated in the
usual way, as for asthma).
Prophylaxis

Annual influenza vaccine. See section 9.2: Adult vaccination.
For frequent severe exacerbations, consult a specialist.
2015
16.6
CHAPTER 16
RESPIRATORY SYSTEM
REFERRAL
»
»
»
For exclusion of a possible foreign body.
For assessment for surgical removal of a bronchiectatic segment.
Major haemoptysis.
16.4 CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
J43/J44
DESCRIPTION
COPD is classified from stage 1 to stage 4. COPD is likely to worsen over
time, even with optimal care.
Regular follow-up is necessary to monitor lung function, symptoms,
exacerbations, co-morbidities, and the need for treatment regimen changes.
Spirometric classification of COPD (FEV1/FVC < 70%) severity based on
% predicted post-bronchodilator FEV1:
Stage 1
Stage 2
Stage 3
Stage 4
Mild COPD
FEV1  80% of predicted.
Moderate COPD
50%  FEV1  80% predicted.
Severe COPD
30%  FEV1  50% predicted.
Very severe COPD
FEV1 < 30%; or FEV1  50% with severe breathlessness at rest
or minimal activity, or the presence of respiratory failure (PaO2 <
8 kPa), and/or cor pulmonale.
GENERAL MEASURES
Patients with clinical COPD should undergo spirometry to confirm and grade
the severity of obstruction.
Patients should be screened for ongoing smoking and advised to stop at
each visit.
MEDICINE TREATMENT
Note: Correct inhaler technique should be demonstrated and checked
regularly.
Management of acute exacerbations
Progression of disease (measured by symptoms and deterioration in lung
function) in COPD is variable, but is greater in patients who experience
COPD exacerbations which are defined as:
» worsening of dyspnoea,
» increased cough,
» increased sputum production or purulence or,
» greater than usual day to day variability of symptoms.
2015
16.7
CHAPTER 16
RESPIRATORY SYSTEM
Severe exacerbations are defined as being sufficiently severe to prompt use
of an oral corticosteroid course and/or an antibiotic. COPD exacerbations
are not always associated with significant decreases in PEF or FEV1, and
are defined by symptoms and, when severe, measures of respiratory failure.
Most are precipitated by viral and/or bacterial infection, and are more
common in winter.
Patients should be admitted if there is a marked increase in dyspnoea,
symptoms disturb eating or sleeping, change in mental status or poor social
circumstances. Causes of worsening symptoms other than an acute
exacerbation of COPD such as cardiac failure, pulmonary embolus, or
pneumonia must be considered.
If available, check blood gases for the presence of hypoxaemia and
hypercapnia. In some patients with long-standing lung disease the drive to
respiration switches from hypercapnia (increases in PaCO2) to hypoxaemia
(level of respiratory failure). In such patients, relief of hypoxaemia with
uncontrolled oxygen therapy may result in hypoventilation, with consequent
rise in PaCO2 to dangerous levels and associated respiratory acidosis
leading to coma and death. For this reason, hypoxaemia should be corrected
using controlled use of supplemental oxygen, starting with a Venturi mask
that delivers not more than 24–28% (take care to avoid using oxygen flow
rates above that recommended for the mask in use). If the patient’s arterial
PaCO2 does not rise, the FiO2 may be increased until a PaO2 of 8kPa is
reached (or oxygen saturation of 90–94%). On the other hand, the FiO2 must
be reduced to ≤ 24% if worsening hypercapnia occurs. Such patients might
require non-invasive ventilation or intubation for mechanical ventilation.
Where blood gases are not readily available, the patient’s clinical status
should be reviewed regularly to check for increasing drowsiness, headache,
or confusion, which may precede coma.
Where resources for mechanical ventilation are scarce, oxygen saturation
targets for patients with long-standing COPD and limited effort tolerance may
be relaxed if the patient is improving clinically.

Salbutamol 5 mg (1 mL 0.5% respiratory solution with 4 mL sodium
chloride 0.9%).
o Nebulise continuously (refill the nebuliser reservoir every 20
minutes) at a flow rate of 6–8 L/minute.
If a poor response to nebulised salbutamol:
ADD

Ipratropium bromide 0.5 mg (UDV) with the first refill of the nebuliser
reservoir.
o Patients who fail to respond within 1 hour must be discussed with a
specialist. (Patients with COPD have fixed airway disease and
unlike asthmatics, PEF is not a reliable measure of their disease).
2015
16.8
CHAPTER 16
RESPIRATORY SYSTEM
Once clinically stabilised, nebulise with:

Salbutamol 5 mg or fenoterol 1.25–2.5 mg
o Repeat 4–6 hourly.
AND

Prednisone, oral, 40 mg immediately.
Follow with:

Prednisone, oral, 40 mg daily for 5 days.
xv
LoE:I
OR
In patients who cannot use oral therapy:

Hydrocortisone, IV, 100 mg 6 hourly until patient can take oral medication.
Once oral medication can be taken, follow with:

Prednisone, oral, 40 mg daily for 5 days.
xvi
o Monitor response and clinical signs.
LoE:I
Antibiotic therapy
Patients with a moderate to severe exacerbation and who have ≥ 2 following
symptoms should receive an antibiotic:
» increased dyspnoea,
» cough, or
» sputum production, especially if purulent.

Amoxicillin, oral, 500 mg 8 hourly for 5 days.
xvii
LoE:III
For patients that have recently been exposed to amoxicillin,
in the last 3 weeks:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 5 days.
xviii
LoE:III
Severe penicillin allergy:
xix
LoE:I

Azithromycin, oral, 500 mg daily for 3 days.
Chronic therapy
COPD with any symptoms.
As initial therapy:

Short acting β2-agonist (SABA) e.g.:

Salbutamol, MDI, 200 mcg 6 hourly as needed using a large volume
spacer.
If no response in symptoms:
Replace with

Long acting β2-agonist (LABA), e.g.:

Formoterol, inhaled 12 mcg 12 hourly. Specialist
initiated.
2015
xx
LoE:I
16.9
CHAPTER 16
RESPIRATORY SYSTEM
For frequent exacerbations (≥ 2 per year):
Replace with

LABA/ICS combination, e.g.: (Specialist initiated)
Salmeterol/fluticasone, inhalation, 25/125 mcg 2 puffs 12
hourly.
xxi
LoE:I
If inadequate control with above therapy:

Theophylline, slow release, oral, 200 mg at night. Specialist consultation.
o Ongoing use of theophylline should be re-evaluated periodically. If
there is no benefit after 12 months discontinue theophylline.
xxii
LoE:II
Corticosteroids
Oral corticosteroids are not recommended for stable COPD.
For acute exacerbations:

Prednisone, oral, 40 mg daily for 5 days.
xxiii
LoE:I
Pre-operative assessment for surgical procedures:
Patients with chronic lung disease are at an increased risk of post-operative
pulmonary complications. Risk is increased with increasing severity of
pulmonary disease, and with upper abdominal or thoracic surgery.
Patients undergoing elective surgery must be optimised pre-operatively by
following the recommended treatment for their disease. Clinical assessment
is sufficient with further investigations such as spirometry, CXR and ABGs
reserved for patients with clinically severe disease/ unstable disease or
where the diagnosis is uncertain. COPD patients should be wheeze free
without dyspnoea on moderate exertion (carrying shopping walking up a
flight of stairs) or a history of frequent exacerbations. As COPD is a disease
characterised by fixed airway obstruction some patients may have
continuous wheezing and will require further pre-operative assessment.
Perioperative oral corticosteroids may be used to gain optimal control but are
not advocated for routine use:

Prednisone, oral, 40 mg daily for not longer than 5 days.
AND
LoE:III
Inhaled therapy must be continued and may be administered
via nebulisation peri-operatively:

SABA, e.g.:
LoE:III

Salbutamol MDI, 200 mcg, 30 minutes pre-intubation.
Prophylaxis

Annual influenza vaccination. See section 9.2: Adult vaccination.
REFERRAL
»
»
2015
Assessment for long-term home-based oxygen therapy, if COPD with
PaO2 < 7.3 kPa and non smoker for at least 3 months,
Recent onset of respiratory failure or signs of cor pulmonale.
16.10
CHAPTER 16
»
»
»
»
»
RESPIRATORY SYSTEM
Symptoms that appear disproportionate to the level of airflow
obstruction, as judged by spirometry or clinical evaluation (absence of
hyperinflation or unusual pattern of symptoms).
Onset < 40 years of age.
COPD with a history of little or no smoking.
Recurrent exacerbations, i.e. ≥ 2 per year.
Failure to respond to treatment.
16.5 LUNG ABSCESS
J85.0/J85.1/J85.2/J85.3
GENERAL MEASURES
Physiotherapy and regular emphasis on postural drainage is of extreme
importance for management.
Instruct patient to do postural drainage for at least 10 minutes, 6 hourly.
Nutritional support.
MEDICINE TREATMENT

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly, until patient apyrexial for
24 hours.
Follow with:
LoE:III

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
Severe penicillin allergy:

Moxifloxacin, IV, 400 mg daily, until patient apyrexial for 24 hours.
Follow with:
xxiv

Moxifloxacin, oral, 400 mg daily.
LoE:II
Duration of therapy
Until no fluid level observed on repeat CXR, usually at least 4 weeks.
REFERRAL
No response to treatment after 21 days of therapy.
Complications, such as empyema or severe haemoptysis.
16.6 PNEUMONIA, COMMUNITY ACQUIRED
J18
Pneumonia is an acute infection of the lung parenchyma. Early appropriate
antibiotic therapy decreases mortality. The decision to hospitalise a patient
and choice of initial antibiotic therapy is guided by age, comorbid diseases
(such as HIV infection, diabetes or chronic respiratory disease), and severity.
Socio-economic circumstances should form part of the clinical assessment
when deciding if a patient is suitable for outpatient treatment.
2015
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RESPIRATORY SYSTEM
GENERAL MEASURES
Diagnosis:
Clinical features include cough, fever, tachypnoea, and signs of
consolidation on chest examination.
CXR usually shows a focal area of opacification or consolidation. Diffuse
bilateral infiltrates in a patient with HIV infection and hypoxaemia is
suspicious of Pneumocystis jirovecii pneumonia.
All patients should be offered HIV testing as HIV infection is associated with
a markedly increased risk of bacterial pneumonia.
Even in clinically classic cases of pneumonia, exclude tuberculosis by
sending sputum for Xpert MTB/RIF®.
A follow-up CXR 4–6 weeks after completion of therapy should be done in all
but very mild cases or in otherwise healthy adults, to ensure complete
resolution of the pneumonia. Follow-up CXRs are indicated earlier only when
complications are suspected, e.g. empyema, abscess, or pneumothorax.
MEDICINE TREATMENT
 Oxygen if hypoxic.
Adequate analgesia for pleuritic chest pain if present. See chapter 21: Pain
Antimicrobial therapy
Duration of antibiotic therapy is guided by clinical response, but should
usually be 5 days.
Prolonged fever and clinical signs may be due to unrecognised TB, or of
complications (such as empyema), or the incorrect choice of antibiotic (e.g.
atypical bacteria), or to an underlying bronchus obstruction (foreign body or
carcinoma). These patients should be further investigated.
Uncomplicated community-acquired pneumonia without features of
severe pneumonia (see below for definition)

Ampicillin, IV, 1 g 6 hourly, until patient apyrexial for 24 hours.
Follow with:
LoE:III

Amoxicillin, oral, 1 g 8 hourly.
xxv
LoE:III
If poor response after 48 hours, consider alternative diagnosis (e.g. TB or
atypical bacterial pneumonia).
Severe penicillin allergy:

Moxifloxacin, oral, 400 mg daily for 5 days.
Patients > 65 years or co-morbid disease (including HIV infection)
2015
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rd

3 generation cephalosporin e.g.:

Ceftriaxone, IV, 2 g daily, until patient apyrexial for 24 hours.
Follow with:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly
for 5 days.
xxvi
LoE:I
xxvii
Severe penicillin allergy:

Moxifloxacin, oral, 400 mg daily.
LoE:III
Severe pneumonia (cyanosis, confusion, hypotension or respiratory rate
>30 breaths/min):

Ceftriaxone, IV, 2 g daily, until patient apyrexial and stable for 24 hours.
xxviii
Follow with:
LoE:III

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly
for 5 days.
AND

Azithromycin, 500mg, slow IV (over 3 hours) daily for 3
xxix
days.
LoE:III
Severe penicillin allergy:

Moxifloxacin, IV, 400 mg daily.
Note: There is no need to add a macrolide, as moxifloxacin has adequate
cover for the atypical bacteria.
HIV infected with bilateral diffuse infiltrates on CXR
Clinically may present with a dry cough of < 12 weeks duration and
significant tachypnoea (CXR may be normal).
Treat as Pneumocystis jirovecii pneumonia (exclude TB):

Cotrimoxazole, oral, 80/400 6 hourly for 21 days.
o < 60 kg 240/1200 mg
o > 60 kg 320/ 1600 mg
(See section 10.2.7 Pneumocystis pneumonia)
If Oxygen Saturation < 90% on pulse oximetry or arterial blood gas
measurement:
ADD

Prednisone, oral, 40 mg 12 hourly for 5 days.
o Followed by Prednisone, oral, 40 mg daily for 5 days.
o Followed by Prednisone, oral, 20 mg daily for 10 days.
xxx
LoE:I
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16.7 PNEUMONIA, ASPIRATION
J69.0
DESCRIPTION
Following aspiration a patient may develop pneumonitis or pneumonia.
Aspiration pneumonitis is more common in previously healthy people who
aspirate gastric acid. Antibiotics will not benefit these patients unless there is
infection present.
Pneumonia following aspiration of gastric contents and/or commensal
organisms from the oropharynx usually occurs in debilitated patients and may
have a more indolent onset with production of purulent sputum and low grade
fever.
There may be solid (food) particles or other foreign bodies aspirated. The
organisms involved are polymicrobial, i.e. Gram-positive and anaerobes.
Aspiration pneumonia should be suspected in patients with episodic or
prolonged decreased level of consciousness, e.g. in alcoholics, drug
overdoses, epileptics, strokes, or those with swallowing problems.
MEDICINE TREATMENT
Antimicrobial therapy
Continue therapy until there are no features of sepsis.

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly, until patient apyrexial and
stable for 24 hours.
Follow with:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
LoE:III
Severe penicillin allergy:

Moxifloxacin, IV, 400 mg daily, until patient apyrexial for 24 hours.
Follow with:
xxxi
LoE:II

Moxifloxacin, oral, 400 mg daily.
If nosocomial infection present (developed > 48 hours post admission),
see section 9.1.3 Hospital-acquired pneumonia.
REFERRAL
»
»
»
»
Hypoxaemia non-responsive to facemask oxygen.
Suspected foreign body aspiration.
Suspected chemical aspiration pneumonia.
Non-resolving pneumonia.
16.8 EMPYEMA
J86.0/J86.9
DESCRIPTION
Pus in the pleural cavity.
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An empyema is always secondary to another process, usually pneumonia,
aspiration pneumonia, lung abscess, tuberculosis, bacteraemia, or a
penetrating chest wall or oesophageal injury.
GENERAL MEASURES
Aspirate and analyse all pleural effusions.
A parapneumonic effusion should be distinguished from an empyema by
biochemical analysis, fluid microscopy and culture.
Empyema, detected early by a low pH (< 7.2) and leucocytosis in pleural
aspirate, and later by a cloudy or clearly infected pleural aspirate, should be
drained completely by chest tube.
The primary management of empyemas is early and complete drainage, by
insertion of an intercostal drain, to prevent long-term complications.
MEDICINE TREATMENT
Antimicrobial therapy
If a complication of pneumonia, antimicrobial therapy as in section 16.6:
Pneumonia, community acquired (but the duration of therapy will need to be
prolonged until drainage is complete).
If not a complication of pneumonia:

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly, until patient apyrexial for
24 hours.
Follow with:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
LoE:III
Treatment duration is until drainage is complete.
Severe penicillin allergy (and not a complication of pneumonia):

Moxifloxacin, IV, 400 mg daily, until patient apyrexial for 24 hours.
Follow with:

Moxifloxacin, oral, 400 mg daily.
LoE:III
Treatment duration is until drainage is complete.
REFERRAL
»
»
Loculated empyema or inadequate drainage.
Chronic empyema with pleural thickening and restrictive lung disease,
requiring surgical decortication.
16.9 TUBERCULOSIS, PULMONARY
A15.0
* A notifiable condition.
Tuberculosis (TB) treatment guidelines are updated regularly. The most
recent National Tuberculosis Control Programme Guidelines should be read
in conjunction with recent guidelines.
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DESCRIPTION
A chronic, granulomatous infection of the lungs caused by M. tuberculosis.
Pulmonary tuberculosis is a serious health problem in South Africa, which is
exacerbated by HIV and multidrug resistant tuberculosis (MDR-TB).
Note: All patients on TB treatment must be entered into a TB register.
Diagnosis
Molecular tests are now routinely available for the diagnosis of M. tuberculosis
and the identification of drug resistant organisms. Two commercial
molecular/PCR tests are currently available in the Public sector: Xpert
MTB/RIF® and the Genotype MTBDRplus® The South African National TB
programme uses the Xpert MTB/RIF® PCR assay as the initial diagnostic test
for patients with suspected tuberculosis, and the assay also gives a result for
rifampicin sensitivity. Genotype MTBDRplus® is a line probe assay (LPA) - it
is used as a confirmatory test for rifampicin resistance detected by Xpert
MTB/RIF® and gives a result for both rifampicin and isoniazid sensitivities. The
LPA is not currently endorsed for use on smear negative sputum, but can be
done directly on smear or culture positive sputum samples.
The diagnosis of pulmonary TB in adults is made on a positive Xpert
MTB/RIF® on sputum. In patients with negative sputum smears, notably HIV
infected patients, Xpert MTB/RIF® is not an adequate ‘rule out’ test and HIV
infected TB suspects who are Xpert MTB/RIF® negative require further
investigation and may need empiric anti-tuberculosis therapy while awaiting
TB cultures.
All patients who are Xpert MTB/RIF® positive require further sputum to be
sent for AFB to allow for monitoring of treatment. Xpert MTB/RIF® should not
be used for monitoring.
All patients with Xpert MTB/RIF® rifampicin resistance require sputum to be
sent for a LPA to confirm rifampicin resistance and the susceptibility to
isoniazid. Send additional sputum for culture and drug susceptibility testing.
All TB patients must be screened for HIV. TB HIV co-infected patients are
eligible for ART and cotrimoxazole prophylaxis regardless of CD4 count.
Sputum induction with nebulised sodium chloride 5% increases the yield of
sputum smear and culture. This may be of special value in the context of HIV
infected persons, as TB frequently presents without cavitation and hence
there is a low sputum mycobacterial yield. Patients with HIV often have
accessible peripheral lymphadenopathy, and a wide needle (e.g. 18G)
aspiration smear for AFBs is often positive. The WHO has recently endorsed
the use of Xpert MTB/RIF® for the diagnosis of TB from extra pulmonary
specimens.
Note: Xpert MTB/RIF® may identify DNA from M. tuberculosis in the
absence of active disease in patients who have recently completed TB
treatment. In these cases, sputum for AFB and culture with sensitivities is
preferred.
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RESPIRATORY SYSTEM
MEDICINE TREATMENT
All patients with active TB who are Xpert MTB/RIF® positive and rifampicin
sensitive, should receive 2 months intensive phase and 4 months
continuation phase (see table below). Patients who are at risk of having
resistant TB (such as a previous episode of TB treatment, prisoners, and
health care workers), should have sputum sent for a LPA or culture and
sensitivity to exclude INH mono resistance, which cannot be detected by
Xpert MTB/RIF®.
National tuberculosis control programme guidelines
Fixed dose drug combinations available:
RH – 150/75 mg
RH – 300/150 mg
RHZE – 150/75/400/275 mg
R – Rifampicin
H – Isoniazid (INH)
Z – Pyrazinamide
E – Ethambutol
Treatment for known or presumed drug sensitive TB
Pre-treatment
Two months
Four months continuation phase
body weight
initial phase
RHZE
RH
RH
(150/75/400/275) (150/75)
(300/150)
30–37 kg
2 tablets
2 tablets
38–54 kg
3 tablets
3 tablets
55–70 kg
4 tablets
2 tablets
71 kg and over
5 tablets
2 tablets
The use of INH may result in the development of a peripheral neuropathy
due to drug-induced pyridoxine deficiency.

Pyridoxine 25 mg daily is recommended prophylactically, with INH, in
patients at high risk of peripheral neuropathy (e.g. HIV, diabetes,
alcoholics), but routine use is not advocated.
Close contacts (particularly children < 5 years of age) of TB patients should
be screened and managed as per National TB Guidelines.
16.10 TUBERCULOSIS, PLEURAL (TB PLEURISY)
A16.5
DESCRIPTION
TB pleurisy is caused by M. tuberculosis entering the pleural cavity, leading
to an inflammatory process accompanied by the formation of an exudative
effusion. It usually presents with a few weeks of pleuritic pain; often
associated with a dry cough, fever, night sweats, weightloss, and, with large
effusions, progressive shortness of breath.
2015
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Diagnosis
It is essential to perform a diagnostic tap of pleural effusions confirmed on a
CXR.
Although a definite diagnosis can only be made by demonstrating the
organisms on smear or culture, or on histology of a pleural biopsy, the
presence of a lymphocytic exudate on pleural fluid analysis is adequate to
start empiric TB therapy in areas with a high TB burden, particularly if the
patient has HIV infection.
All patients started on empiric TB therapy for pleural TB must be followed up
closely; failure to respond as expected must prompt investigations to exclude
other causes. Once TB therapy is started, signs and symptoms should
resolve within 2 weeks. Radiographic improvement is usually evident by 6
weeks, but complete resorption can take up to 4 months. However, pleural
thickening may persist. A pleural biopsy at initial presentation is strongly
recommended for the following patients: older than 50 years, or risk factors
for malignancy, or not presenting with typical TB symptoms.
Treatment is as for pulmonary TB.
A weight gain of 2% at 1 month and 5% at 2 months of TB therapy can be
expected.
Note: Total drainage by aspiration or under-water tube is not needed. For
large effusions that cause dyspnoea drain a maximum of 1 litre at a time.
However, a TB pleural empyema must be drained by intercostal under-water
tube-drainage.
REFERRAL
»
»
»
Non-resolving effusions. Suspect an incorrect diagnosis of TB pleurisy if
the effusion does not improve on the CXR after 3 months of
treatment or if the patient deteriorates.
Loculated TB empyema, not resolving after intercostal underwater tube
drainage and needing assessment for surgical drainage.
Bronchopleural fistula, not resolving after 6 weeks
16.11 DRUG-RESISTANT TB
Z16.34
16.11.1 INH MONORESISTANT TB
Z16.341
MEDICINE TREATMENT
Patients with confirmed INH monoresistant TB can be successfully treated
with:

Rifampicin, oral, 10 mg/kg daily.
AND

Ethambutol, oral, 15 mg/kg daily.
2015
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RESPIRATORY SYSTEM
AND

Pyrazinamide, oral, 25 mg/kg daily.
xxxii
LoE:III
Where single medicines are not available or the pill burden
is too high a fixed dose combination of RHZE dosed as per weight may be
used.
Treatment should be given for at least 6 months after sputum culture
conversion. In the absence of sputum culture results the duration of therapy
should be 6-9 months depending on clinical response.
16.11.2 MULTIDRUG-RESISTANT TB
Z16.342
Never treat for MDR TB without laboratory confirmation, either by
molecular or phenotypic (culture and sensitivity) results.
All cases should be discussed with a regional specialist centre.
Refer to the latest National Department of Health guidelines for the
management of drug-resistant TB.
DESCRIPTION
Multidrug resistant tuberculosis (MDR TB) is diagnosed when there is in vitro
resistance of M. tuberculosis against, at least, rifampicin and isoniazid.
MDR TB is diagnosed exclusively on culture and sensitivity assays or rapid
molecular tests. Xpert MTB/RIF® only tests for rifampicin resistance and not
isoniazid resistance. However, rifampicin resistance by Xpert MTB/RIF® is
sufficient to start a patient on MDR treatment pending confirmation of MDR
TB by LPA.
All patients with HIV and TB (including MDR TB) qualify for ART irrespective
of CD4 count. Avoid a TDF-containing regimen whilst on aminoglycoside
therapy, if possible, as both medicines are nephrotoxic.
GENERAL MEASURES
Screen all close contacts for signs and symptoms of TB and by sputum
Xpert MTB/RIF® to detect early disease. Contacts with positive results
should be treated according to the rifampicin sensitivity, either as sensitive
TB or MDR TB.
MEDICINE TREATMENT
MDR TB prophylaxis
The effectiveness of preventive therapy in adults exposed to MDR TB
bacteria is not known.
In the absence of evidence, prophylaxis is not recommended in adults.
2015
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RESPIRATORY SYSTEM
Treatment
Prolonged treatment, for at least 18 months after culture conversion, is
required in patients diagnosed with MDR TB.
Management of MDR TB should be conducted in dedicated MDR TB clinics
and hospitals with appropriate infection control measures. Patients
diagnosed with MDR TB who are smear positive should be hospitalised for
up to eight weeks or until they become smear negative on two consecutive
tests.
Smear negative, culture positive patients should be started on MDR TB
treatment in the community. MDR TB treatment should not be delayed while
waiting for a bed or confirmation of MDR TB by LPA.
Standardised regimen for treatment of MDR tuberculosis in South Africa.
The standardised regimen consists of at least 6 months intensive phase
(also known as injectable phase) with five medicines taken 6 times a week;
followed by a continuation phase with four medicines taken 6 times a week
and continued until 18 months after TB culture conversion.
Intensive phase: At least 6 months, guided by TB culture conversion (to be
continued for 4 months after TB culture conversion).
<33 kg
33–50 kg
50–65 kg
>65 kg
Kanamycin*
15 mg/kg
15 mg/kg
15 mg/kg
1g
(max:1 g)
Moxifloxacin
400 mg
400 mg
400 mg
400 mg
Ethionamide** 15–20 mg/kg 500 mg
750 mg
750 mg–1 g
Terizidone
15–20 mg/kg 750 mg
750 mg
750 mg–1 g
Pyrazinamide 30–40 mg/kg 1 g–1750 mg 1 750 mg–2 g 2 g–2 500 mg
*If kanamycin is contraindicated (e.g. deafness, renal failure) or toxicity
develops, replace with bedaquiline (requires approval from a Drug
Resistance TB Committee).
**If the LPA shows katG mutation use ethionamide. If there is the inhA
mutation use high dose INH (15 mg/kg) in place of ethionamide. If both
mutations are present use bedaquiline (requires approval from a Drug
xxxiii
Resistance TB Committee).
LoE:III
Consult the most recent National Department of Health Policy: Introduction
of new drugs and drug regimens for the management of drug-resistant
tuberculosis: Policy Framework, for guidance on bedaquiline.
Pyridoxine
Both ethionamide and terizidone may cause pyridoxine deficiency .
All patients receiving terizidone should be given 50 mg of pyridoxine for
every 250 mg of terizidone.
2015
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
RESPIRATORY SYSTEM
Pyridoxine, oral, 150 mg daily.
LoE:III
Continuation phase: at least 18 months after TB culture conversion
< 33 kg
33–50 kg
50–65 kg
> 65 kg
Moxifloxacin
400 mg
400 mg
400 mg
400 mg
Ethionamide** 15–20 mg/kg
500 mg
750 mg
750 mg–1 g
Terizidone
15–20 mg/kg
750 mg
750 mg
750 mg–1 g
Pyrazinamide 30–40 mg/kg
1 g–1750 mg 1 750 mg–2 g 2 g–2 500 mg
Note:
» Patients with resistance to the above medicines should all be treated
in specialised centres approved by the Department of Health.
» Do a pregnancy test at baseline.
» Birth control should be used in women of a child-bearing age, as some of
the agents are teratogenic.
» In pregnant women, the benefits of MDR management outweigh the
teratogenicity risks.
» Patients with renal impairment should be referred for replacement of
kanamycin by bedaquiline and for dose adjustments of some other
drugs.
» Conduct regular hearing tests/audiograms and renal function monitoring
on patients on aminoglycosides and refer for replacement with
bedaquiline if hearing loss (initially high frequency) or renal impairment is
detected.
» Kanamycin can cause hypokalaemia and potassium levels must be
checked monthly during the injectable phase.
» Perform TSH blood test at baseline, then 6 monthly to monitor for
hypothyroidism associated with ethionamide.
XDR TB and Pre-XDR TB
Patients with MDR TB who in addition have resistance to any
nd
fluoroquinolone and at least one of the 2 line injectables (kanamycin,
amikacin, or capreomycin). Pre-XDR TB is defined as MDR TB plus
resistance to either a fluoroquinolone or an injectable.
Confirmation of XDR TB requires drug susceptibility testing.
Patients with XDR TB need to be referred to a TB hospital. Infection control
to prevent airborne transmission is essential to prevent nosocomial
transmission.
Individualised regimens based on susceptibility tests and treatment history
are recommended to achieve a regimen with a minimum of 4–5 effective
medicines for minimum duration of 18 months after sputum culture
conversion.
2015
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Salbutamol nebulisation: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,
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ix
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xi
Ceftriaxone: Carratalà J, Garcia-Vidal C, Ortega L, Fernández-Sabé N, Clemente M, Albero G, López M,
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Prins JM, Slee PH, Kaasjager K, Hoepelman AI. Effectiveness of early switch from intravenous to oral antibiotics in
severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006 Dec 9;333(7580):1193.
http://www.ncbi.nlm.nih.gov/pubmed/17090560
Ceftriaxone, IV: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group.
British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
Ceftriaxone, IV: Perry TR, Schentag JJ. Clinical use of ceftriaxone: a pharmacokinetic-pharmacodynamic
perspective on the impact of minimum inhibitory concentration and serum protein binding. Clin Pharmacokinet.
2001;40(9):685-94. http://www.ncbi.nlm.nih.gov/pubmed/11605716
2015
16.22
CHAPTER 16
RESPIRATORY SYSTEM
Ceftriaxone, IV: NICD pneumococci susceptibility data for amoxicillin for the period 2005-2014 [E-mail
communication]
xii
Amoxicillin/clavulanic acid: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF
Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
Amoxicllin/clavulanic acid: NICD pneumococci susceptibility data for amoxicillin for the period 2005-2014 [Email communication]
Amoxicillin/clavulanic acid: Kiffer CR, Pignatari AC. Pharmacodynamic evaluation of commonly prescribed
oral antibiotics against respiratory bacterial pathogens. BMC Infect Dis. 2011 Oct 25;11:286.
http://www.ncbi.nlm.nih.gov/pubmed/22026724
xiii
Ciprofloxacin, oral: Chan TH, Ho SS, Lai CK, Cheung SW, Chan RC, Cheng AF, Chan CH. Comparison of oral
ciprofloxacin and amoxycillin in treating infective exacerbations of bronchiectasis in Hong Kong. Chemotherapy.
1996 Mar-Apr;42(2):150-6. http://www.ncbi.nlm.nih.gov/pubmed/8697891
Ciprofloxacin, oral: Chen TC, Lu PL, Lin CY, Lin WR, Chen YH. Fluoroquinolones are associated with delayed
treatment and resistance in tuberculosis: a systematic review and meta-analysis. Int J Infect Dis. 2011
Mar;15(3):e211-6. http://www.ncbi.nlm.nih.gov/pubmed/21195001
xiv
Moxifloxacin, IV: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group.
British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
xv
Prednisone: Leuppi JD., Schuetz P., Bingisser R., Bodmer M., Briel M., Drescher T., Duerring U., Henzen C.,
Leibbrandt Y., Maier S., Miedinger D., Muller B., Scherr A., Schindler C., Stoeckli R., Viatte S., von Garnier C.,
Tamm J. 2013. Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive
Pulmonary Disease. The REDUCE Randomized Clinical Trial. JAMA. Vol 309(21): 2223-2231
http://www.ncbi.nlm.nih.gov/pubmed/23695200
xvi
Prednisone: Leuppi JD., Schuetz P., Bingisser R., Bodmer M., Briel M., Drescher T., Duerring U., Henzen C.,
Leibbrandt Y., Maier S., Miedinger D., Muller B., Scherr A., Schindler C., Stoeckli R., Viatte S., von Garnier C.,
Tamm J. 2013. Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive
Pulmonary Disease. The REDUCE Randomized Clinical Trial. JAMA. Vol 309(21): 2223-2231
http://www.ncbi.nlm.nih.gov/pubmed/23695200
xvii
Amoxicillin, oral: NICE COPD Guidelines, 2010. https://www.nice.org.uk/guidance/cg101
xviii
Amoxicillin/clavulanic acid: Allegra L, Blasi F, de Bernardi B, Cosentini R, Tarsia P. Antibiotic treatment and
baseline severity of disease in acute exacerbations of chronic bronchitis: a re-evaluation of previously published
data of a placebo-controlled randomized study. Pulm Pharmacol Ther. 2001;14(2):149-55.
http://www.ncbi.nlm.nih.gov/pubmed/11273797
Amoxicillin/clavulanic acid, oral: Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA.
Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane
Database Syst Rev. 2012 Dec 12;12:CD010257. http://www.ncbi.nlm.nih.gov/pubmed/23235687
xix
Azithromycin, oral: Zervos M, Martinez FJ, Amsden GW, Rothermel CD, Treadway G. Efficacy and safety of 3day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.
Int J Antimicrob Agents. 2007 Jan;29(1):56-61. http://www.ncbi.nlm.nih.gov/pubmed/17189096
Azithromycin, oral: Amsden GW, Baird IM, Simon S, Treadway G. Efficacy and safety of azithromycin
vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis. Chest. 2003
Mar;123(3):772-7. http://www.ncbi.nlm.nih.gov/pubmed/12628877
Azithromycin, oral: SAMF, 2014.
xx
Formoterol inhaler: Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist
in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database
Syst Rev. 2012 Sep12;9:CD006829. http://www.ncbi.nlm.nih.gov/pubmed/22972099
xxi
Long-acting β2-agonist/corticosteroid combination inhaler: Nannini LJ, Poole P, Milan SJ, Kesterton A.
Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for
chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013 Aug 30;8:CD006826.
http://www.ncbi.nlm.nih.gov/pubmed/23990350
Long-acting β2-agonist/corticosteroid combination inhaler: Kew KM, Dias S, Cates CJ. Long-acting inhaled
therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis. Cochrane Database
Syst Rev. 2014 Mar 26;3:CD010844. http://www.ncbi.nlm.nih.gov/pubmed/24671923
xxii
Theophylline: Ford PA, Durham AL, Russell RE, Gordon F, Adcock IM, Barnes PJ. Treatment effects of lowdose theophylline combined with an inhaled corticosteroid in COPD. Chest. 2010 Jun;137(6):1338-44. doi:
10.1378/chest.09-2363. Epub 2010 Mar 18. http://www.ncbi.nlm.nih.gov/pubmed/20299628
Theophylline: Cosio BG, Iglesias A, Rios A, Noguera A, Sala E, Ito K, Barnes PJ, Agusti A. Low-dose
theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax. 2009
May;64(5):424-9. http://www.ncbi.nlm.nih.gov/pubmed/19158122
xxiii
Prednisone: Burge P.S., Calverley P.M.A., Jones P.W., Spencer S., Anderson J.A., on behalf of the ISOLDE
Study Group. 2003. Prednisolone response in patients with chronic obstructive pulmonary disease: results from the
ISOLDE study. Thorax. Vol 58: 654-658 http://www.ncbi.nlm.nih.gov/pubmed/12885977
xxiv
Moxifloxacin: Ott SR, Allewelt M, Lorenz J, Reimnitz P, Lode H; German Lung Abscess Study Group.
Moxifloxacin vs ampicillin/sulbactam in aspiration pneumonia and primary lung abscess. Infection. 2008
Feb;36(1):23-30. http://www.ncbi.nlm.nih.gov/pubmed/18231720
xxv
Amoxicillin: Primary Healthcare STGs and EML, 2014. http://www.health.gov.za/
2015
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xxvi
Ceftriaxone: Carratalà J, Garcia-Vidal C, Ortega L, Fernández-Sabé N, Clemente M, Albero G, López M,
Castellsagué X, Dorca J, Verdaguer R, Martínez-Montauti J, Manresa F, Gudiol F. Effect of a 3-step critical
pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia:
a randomized controlled trial. Arch Intern Med. 2012 Jun 25;172(12):922-8.
http://www.ncbi.nlm.nih.gov/pubmed/22732747
Ceftriaxone: Oosterheert JJ, Bonten MJ, Schneider MM, Buskens E, Lammers JW, Hustinx WM, Kramer MH,
Prins JM, Slee PH, Kaasjager K, Hoepelman AI. Effectiveness of early switch from intravenous to oral antibiotics in
severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006 Dec 9;333(7580):1193.
http://www.ncbi.nlm.nih.gov/pubmed/17090560
Ceftriaxone, IV: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group.
British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
Ceftriaxone, IV: Perry TR, Schentag JJ. Clinical use of ceftriaxone: a pharmacokinetic-pharmacodynamic
perspective on the impact of minimum inhibitory concentration and serum protein binding. Clin Pharmacokinet.
2001;40(9):685-94. http://www.ncbi.nlm.nih.gov/pubmed/11605716
Ceftriaxone, IV: NICD pneumococci susceptibility data for amoxicillin for the period 2005-2014 [E-mail
communication]
xxvii
Amoxicillin/clavulanic acid: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF
Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
Amoxicllin/clavulanic acid: NICD pneumococci susceptibility data for amoxicillin for the period 2005-2014 [Email communication]
Amoxicillin/clavulanic acid: Kiffer CR, Pignatari AC. Pharmacodynamic evaluation of commonly prescribed
oral antibiotics against respiratory bacterial pathogens. BMC Infect Dis. 2011 Oct 25;11:286.
http://www.ncbi.nlm.nih.gov/pubmed/22026724
xxviii
Ceftriaxone, IV: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline
Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
http://www.ncbi.nlm.nih.gov/pubmed/20627931
Ceftriaxone, IV: Perry TR, Schentag JJ. Clinical use of ceftriaxone: a pharmacokinetic-pharmacodynamic
perspective on the impact of minimum inhibitory concentration and serum protein binding. Clin Pharmacokinet.
2001;40(9):685-94. http://www.ncbi.nlm.nih.gov/pubmed/11605716
Ceftriaxone, IV: NICD pneumococci susceptibility data for amoxicillin for the period 2005-2014 [E-mail
communication]
xxix
Azithromycin, IV: Contract circular HP02-2015AI. http://www.health.gov.za/
xxx
Prednisone: Ewald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for
Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015 Apr
2;4:CD006150. http://www.ncbi.nlm.nih.gov/pubmed/25835432
Prednisone: Bozzette SA, Sattler FR, Chiu J, Wu AW, Gluckstein D, Kemper C, Bartok A, Niosi J, Abramson I,
Coffman J, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii
pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med.
1990 Nov 22;323(21):1451-7. http://www.ncbi.nlm.nih.gov/pubmed/2233917
xxxi
Moxifloxacin: Sun T, Sun L, Wang R, Ren X, Sui DJ, Pu C, Ren Y, Liu Y, Yang Z, Li F. Clinical efficacy and
safety of moxifloxacin versus levofloxacin plus metronidazole for community-acquired pneumonia with aspiration
factors. Chin Med J (Engl). 2014;127(7):1201-5. http://www.ncbi.nlm.nih.gov/pubmed/24709166
Moxifloxacin: Ott SR, Allewelt M, Lorenz J, Reimnitz P, Lode H; German Lung Abscess Study Group.
Moxifloxacin vs ampicillin/sulbactam in aspiration pneumonia and primary lung abscess. Infection. 2008
Feb;36(1):23-30. http://www.ncbi.nlm.nih.gov/pubmed/18231720
xxxii
Rifampicin, oral: Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM, Osmond
D, Hopewell PC, Nahid P. Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant
tuberculosis. Clin Infect Dis. 2009 Jan 15;48(2):179-85. http://www.ncbi.nlm.nih.gov/pubmed/19086909
doi: 10.1086/595689. PubMed PMID: 19086909
Rifampicin, oral: Wang TY, Lin SM, Shie SS, Chou PC, Huang CD, Chung FT, Kuo CH, Chang PJ, Kuo
HP. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazidmonoresistant tuberculosis. PLoS One. 2014 Jan 22;9(1):e86316. http://www.ncbi.nlm.nih.gov/pubmed/24466020
Rifampicin, oral: National Department of Health. 2014. National Tuberculosis Management Guidelines. South
Africa. http://www.health.gov.za/
Ethambutol, oral: Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM, Osmond
D, Hopewell PC, Nahid P. Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant
tuberculosis. Clin Infect Dis. 2009 Jan 15;48(2):179-85. http://www.ncbi.nlm.nih.gov/pubmed/19086909
Ethambutol, oral: Wang TY, Lin SM, Shie SS, Chou PC, Huang CD, Chung FT, Kuo CH, Chang PJ, Kuo
HP. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazidmonoresistant tuberculosis. PLoS One. 2014 Jan 22;9(1):e86316. http://www.ncbi.nlm.nih.gov/pubmed/24466020
Ethambutol, oral: National Department of Health. 2014. National Tuberculosis Management Guidelines. South
Africa. http://www.health.gov.za/
Pyrazinamide, oral: Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM,
Osmond D, Hopewell PC, Nahid P. Clinical characteristics and treatment outcomes of patients with isoniazidmonoresistant tuberculosis. Clin Infect Dis. 2009 Jan 15;48(2):179-85.
http://www.ncbi.nlm.nih.gov/pubmed/19086909
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16.24
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Pyrazinamide, oral: Wang TY, Lin SM, Shie SS, Chou PC, Huang CD, Chung FT, Kuo CH, Chang PJ, Kuo
HP. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazidmonoresistant tuberculosis. PLoS One. 2014 Jan 22;9(1):e86316. http://www.ncbi.nlm.nih.gov/pubmed/24466020
Pyrazinamide, oral: National Department of Health. 2014. National Tuberculosis Management Guidelines. South
Africa. http://www.health.gov.za/
xxxiii
Bedaquiline: National Department of Health: Introduction of new drugs and drug regimens for the management
of drug-resistant tuberculosis in South Africa: policy framework, v1.1, June 2015. http://www.health.gov.za/
Bedaquiline: World Health Organisation. The Use of Bedaquiline in the Treatment of Multidrug-Resistant
Tuberculosis: Interim Policy Guidance. Geneva: World Health Organization; 2013. Executive summary. Available
from: http://www.ncbi.nlm.nih.gov/books/NBK154129/
Ethionamide: National Department of Health: Introduction of new drugs and drug regimens for the management
of drug-resistant tuberculosis in South Africa: policy framework, v1.1, June 2015. http://www.health.gov.za/
Isoniazid: National Department of Health: Introduction of new drugs and drug regimens for the management of
drug-resistant tuberculosis in South Africa: policy framework, v1.1, June 2015. http://www.health.gov.za/
2015
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EAR, NOSE AND THROAT DISORDERS
17.1 EPIGLOTTITIS
J05.1
DESCRIPTION
Acute epiglottitis can result in severe, sudden or progressive airway
obstruction.
Acute epiglottitis can be caused by bacteria (e.g. H. influenzae), viruses (e.g.
herpes simplex) and non-infectious insults (trauma, chemicals, heat).
GENERAL MEASURES
Airway management may require urgent specialist advice.
Adequate hydration.
MEDICINE TREATMENT
Humidified oxygen.
Antibiotic therapy
Total duration of therapy: 10 days
Intravenous therapy:
rd

3 generation cephalosporin, e.g.:

Ceftriaxone, IV, 1 g daily.
Switch early to oral therapy to complete the 10 day course:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
Severe penicillin allergy to amoxicillin/clavulanic acid, oral:

Macrolide, e.g.:

Azithromycin, oral, 500 mg daily for 3 days.
i
LoE:III
Acute stage
Imminent airway obstruction:

Hydrocortisone, IV, 100 mg immediately as a single dose.
ii
AND
LoE:III

Adrenaline (epinephrine) 1:1 000, 1 mL nebulised.
o Dilute to 5 mL with sodium chloride 0.9% and administer 4–6 hourly.
iii
LoE:III
2015
17.1
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17.2 RHINITIS, ALLERGIC, PERSISTENT
J30.4
DESCRIPTION
Allergic rhinitis is an allergic inflammation of the nasal airways. Signs and
symptoms include rhinorrhea, itching, sneezing, nasal congestion and
obstruction, conjunctival swelling and erythema, puffy eyes, swollen nasal
turbinates, and middle ear effusion.
GENERAL MEASURES
Avoid allergens and irritants.
Provide education on the correct technique of administering topical
medicines. Incorrect technique is a common cause of treatment failure.
MEDICINE TREATMENT


Corticosteroid, e.g.
Budesonide topical, aqueous nasal solution, 1 spray of 100 mcg in each
nostril 12 hourly.
o Aim the nozzle laterally and upwards (aim for the eye) and not to
the back of the throat.
o Do not sniff vigorously.
iv
LoE:III
If symptoms persist despite an adequate trial of topical corticosteroids
administered with the correct technique:
ADD

Cetirizine, oral, 10 mg daily.
For relief of nasal blockage:

Topical nasal decongestants, e.g.:

Oxymetazoline 0.05%, intranasal, administered 8 hourly for a maximum
of 5 days.
Failure of the above:
ADD

Prednisone, oral, 30 mg daily for 5 days whilst continuing the topical
steroid.
17.3 SINUSITIS, BACTERIAL, COMPLICATED
J01.9
DESCRIPTION
Acute bacterial sinusitis complicated by extension to the orbit or
intracranially.
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17.2
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Extension to the orbit causes orbital cellulitis or orbital periosteal abscess,
both of which may present with pain on eye movement, partial or complete
visual loss (which can be irreversible), ophthalmoplegia, and proptosis.
Eyelid oedema and erythema is usually present, but external signs of
inflammation may be absent. Intracranial extension may cause meningitis,
subdural empyema, brain abscess, or thrombosis of cavernous sinus/cortical
veins.
In immunosuppressed or diabetic patients presenting with features of
bacterial sinusitis also consider fungal infections such as mucormycosis.
Features suggesting mucormycosis include necrosis of the nasal or palatal
mucosa, and orbital or cerebral involvement.
MEDICINE TREATMENT

Ceftriaxone, IV, 2 g 12 hourly and refer.
URGENT REFERRAL
»
»
Proptosis.
Ophthalmoplegia.
REFERRAL
»
»
After initiating antimicrobial therapy, refer for a CT scan, to a centre
where an appropriate surgical specialist, i.e. ophthalmologist, ENT
specialist or neurosurgeon, is available,
Suspected fungal sinusitis.
17.4 OTITIS MEDIA, ACUTE
H66.9
DESCRIPTION
Inflammation of the middle ear of rapid onset.
MEDICINE TREATMENT
In previously untreated patients:

Amoxicillin, oral, 500 mg 8 hourly for 5 days
Patients not responding to amoxicillin:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 5 days
Severe penicillin allergy:

Macrolide, e.g.:

Azithromycin, oral, 500 mg daily for 3 days.
v
LoE:III
For patients with upper respiratory tract congestion, consider:

Cetirizine, oral, 10 mg daily for 10 days.
2015
17.3
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EAR, NOSE AND THROAT DISORDERS
For pain:

NSAID, oral: e.g.

Ibuprofen, oral, 400 mg 8 hourly with meals.
LoE:III
REFERRAL
»
»
»
»
No response after 5 days treatment.
No pain relief despite treatment.
Bulging eardrum, not responding to treatment after 24 hours.
Recurrent otitis media.
17.5 OTITIS MEDIA, CHRONIC, SUPPURATIVE
H66.3
DESCRIPTION
A purulent discharge from the ear for more than 2 weeks.
If the eardrum has been ruptured for 2 weeks or longer, a secondary infection
with multiple organisms usually occurs. Multiple organism infection often makes
oral antibiotic treatment ineffective and patients may need to be referred.
TB is an important cause of a chronically discharging ear in South Africa.
If pain is present, suspect another condition or complications.
Note:
» A chronically draining ear can only heal if it is dry.
» Drying the ear is time consuming but is the most effective treatment.
» HIV status should be established in chronic otitis media.
GENERAL MEASURES
Dry mopping is the most important part of the treatment. It should be
demonstrated to the patient.
» Roll a piece of clean absorbent cloth into a wick.
» Carefully insert the wick into the ear with twisting action.
» Remove the wick and replace with a clean dry wick.
» Repeat this until the wick is dry when removed.
Do not leave anything in the ear.
Avoid getting the inside of the ear wet while swimming and bathing.
Exclude TB as a cause.
MEDICINE TREATMENT
After cleaning and drying the ear:

Acetic acid 2% in alcohol, topical, 3–4 drops instilled into the ear every 6
hours for 5 days.

Ciprofloxacin, oral, 500 mg 12 hourly for 5 days.
REFERRAL
»
2015
Focal neurological signs such as facial nerve palsy.
17.4
CHAPTER 17
»
»
»
»
»
EAR, NOSE AND THROAT DISORDERS
Vomiting or drowsiness.
Painful swelling behind the ear.
No improvement after 4 weeks.
Any attic perforation.
Any perforation not progressively improving after 3 months or closed by
6 months, even if dry.
Moderate or severe hearing loss.
Effusion.
»
»
17.6 MASTOIDITIS
H70.9
DESCRIPTION
Infection of the mastoid air cells, usually complicating otitis media. Most
patients have evidence of external inflammation over the mastoid bone.
Diagnosis should be confirmed radiographically, preferably by CT scan.
MEDICINE TREATMENT

Ceftriaxone, IV, 2 g 12 hourly.
REFERRAL
After initiating antimicrobial therapy, refer to a centre where mastoidectomy
can be performed.
17.7 OTITIS EXTERNA
17.7.1 OTITIS EXTERNA, NECROTISING
H60.9
DESCRIPTION
Severe otalgia and otorrhoea which is unresponsive to medical therapy. In later
stages cranial nerve palsies can occur. Most common pathogen: P. aeruginosa.
Necrotising otitis externa is typically associated with elderly diabetics or
other immunocompromised patients.
GENERAL MEASURES
Debridement as indicated.
Insert a dry wick such as a dried sponge, into the canal under direct vision.
Remove the wick 2 days later, and replace if necessary.
MEDICINE TREATMENT

Ciprofloxacin, oral, 750 mg 12 hourly, and refer.
2015
LoE:III
17.5
CHAPTER 17
EAR, NOSE AND THROAT DISORDERS
REFERRAL
»
»
»
For surgical debridement of necrotic bone in non-responders.
All cases to a centre where CT scan of the affected area can be done to
assess the extent of the disease.
Cranial nerve palsies.
17.8 ABSCESS, PERITONSILLAR
J36
DESCRIPTION
Peritonsillar abscess or quinsy is a collection of pus lateral to the tonsil, i.e.
underneath it pushing it toward the midline. It typically presents with trismus
and sore throat. Other features include:
» unilateral throat pain
» dysphagia
» drooling
» muffled voice
» fever
SURGICAL MEASURES
Drainage of pus is the most important intervention.
There are 3 main methods:
» needle aspiration of pus
» incision and drainage
» abscess tonsillectomy, either unilateral or bilateral.
MEDICINE TREATMENT
Antibiotic therapy
Total duration of therapy: 10 days.
Intravenous therapy:
 Benzylpenicillin (penicillin G), IV, 2 million units 6 hourly.
AND
 Metronidazole, IV, 500 mg 8 hourly.
Switch to oral therapy as soon as possible:
 Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly.
Severe penicillin allergy:
 Clindamycin, IV, 600 mg 8 hourly.
Follow with:
 Clindamycin, oral, 450 mg 8 hourly.
For pain:

NSAID, oral: e.g.

Ibuprofen, oral, 400 mg 8 hourly with meals.
2015
17.6
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EAR, NOSE AND THROAT DISORDERS
REFERRAL
Referral for ENT and/or anaesthetic review:
» Signs of airway compromise (e.g. stridor)).
» Suspicion of infective spread beyond the peritonsillar space.
17.9 VERTIGO, ACUTE
R42
DESCRIPTION
An acute syndrome, consisting of vertigo, nystagmus, nausea, vomiting and
postural instability. It is important to differentiate between peripheral and
central causes of vestibular dysfunction.
Peripheral causes
Patients frequently present with vertigo, which is most often rotational, with
nystagmus. The onset is usually sudden and often intermittent. Associated
abnormalities of hearing may be present. Aetiology includes benign
paroxysmal positional vertigo (confirm with a positive Dix-Hallpike test),
aminoglycoside vestibular toxicity, and vestibular neuritis.
Central causes
It is essential to conduct a thorough neurological examination in patients with
vertigo, looking specifically for signs of brainstem or cerebellar dysfunction.
Aetiology includes cerebellar stroke and space occupying lesions of the
posterior cranial fossa.
GENERAL MEASURES
It is essential to find the cause and treat appropriately. Patients with
suspected central causes should be referred for neuro-imaging and possible
neurosurgical management.
Benign positional vertigo
Good results may be achieved with particle relocation manoeuvres, such as
the Epley manoeuvre. In a third of patients, symptoms recur after 1 year and
repeat manoeuvres may be required.
MEDICINE TREATMENT
This is only for symptomatic relief and is determined by the aetiology.
Discontinue all medication as soon as symptoms subside as the medication
itself may cause vertigo due to involvement of the unaffected side.

Promethazine, oral, 10 mg 8 hourly.
o May be increased to 20 mg 8 hourly if necessary.
Note: This is sedating and patients should not drive or operate heavy
machinery.
vi
LoE:I
2015
17.7
CHAPTER 17
EAR, NOSE AND THROAT DISORDERS
Cerebellar stroke
See section 14.1: Cerebrovascular Disease.
REFERRAL
»
»
Suspected intracranial mass lesions or cerebellar stroke.
Patients not responding to therapy for exclusion of alternative aetiology.
References:
i
Azithromycin, oral: Wasserman S, Boyles T, Mendelson M. South African antibiotic stewardship programme
(SAASP): A pocket guide to antibiotic prescribing for adults in South Africa, 2015.
http://www.fidssa.co.za/images/SAASP_Antibiotic_Gudidelines_2015.pdf
ii
Hydrocortisone, IV:: Riffat F, Jefferson N, Bari N, McGuinness J. Acute supraglottitis in adults. Ann Otol Rhinol
Laryngol. 2011 May;120(5):296-9. http://www.ncbi.nlm.nih.gov/pubmed/21675584
Hydrocortisone, IV: Mayo-Smith MF, Spinale JW, Donskey CJ, Yukawa M, Li RH, Schiffmann FJ. Acute
epiglottitis: an 18-year old experience in Rhode Island. Chest 1995;108:1640–7.
http://www.ncbi.nlm.nih.gov/pubmed/7497775
Hydrocortisone, IV: Bizaki AJ, Numminen J, Vasama JP, Laranne J, Rautiainen M. Acute supraglottitis in adults
in Finland: review and analysis of 308 cases. Laryngoscope. 2011 Oct;121(10):2107-13.
http://www.ncbi.nlm.nih.gov/pubmed/21898436
Hydrocortisone, IV: Wick R, Ballmer PE, Haller A. Acute epiglottitis in adults. Swiss Med Wkly 2002; 132: 541–
7. http://www.ncbi.nlm.nih.gov/pubmed/12557859
Hydrocortisone, IV: Hafidh MA, Sheahan P, Keogh I, Walsh RM. Acute epiglottitis in adults: a recent experience
with 10 cases. J Laryngol Otol. 2006 Apr;120(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/16623975
iii
Adrenaline (epinephrine), nebulisation: Wick R, Ballmer PE, Haller A. Acute epiglottitis in adults. Swiss Med
Wkly 2002; 132: 541–7. http://www.ncbi.nlm.nih.gov/pubmed/12557859
iv
Budesonide topical, aqueous nasal solution: Contract circular HP07-2014DAI. http://health.gov.za
v
Azithromycin, oral: Contract circular HP09-2014SD. http://health.gov.za
vi
Promethazine, oral: James AL, Burton MJ. Betahistine for Menière's disease or syndrome. Cochrane Database
Syst Rev. 2001;(1):CD001873. http://www.ncbi.nlm.nih.gov/pubmed/11279734
2015
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EYE DISORDERS
18.1 CONJUNCTIVITIS
H10.9
DESCRIPTION
Inflammation of the conjunctiva, usually due to allergy or infection (viral or
bacterial).
Conjunctivitis is usually bilateral. Other causes of a red eye are often unilateral.
The condition is self-limiting and usually resolves within 14 days.
GENERAL MEASURES
If it is due to an infection, counsel on the importance of:
» frequent hand washing,
» using separate linen, towels and washcloths, and
» avoiding direct contact with infected material or individuals.
Contact lenses should not be worn if conjunctivitis is present or during a
course of topical therapy. Soft lenses should not be worn within 24 hours of
instilling eye drops containing the preservative benzalkonium chloride.
18.1.1 CONJUNCTIVITIS, ADENOVIRAL
H13.1*/B30.1+
DESCRIPTION
Adenovirus is a common cause of infective conjunctivitis. It may be unilateral
but is usually bilateral.
Clinical features:
» Viral conjunctivitis may be associated with an upper respiratory tract
infection.
» A burning, sandy, or gritty feeling in the eyes.
» Morning crusting followed by watery discharge.
» Preauricular lymphadenopathy may be present.
The condition is self-limiting but eye irritation and discharge may get worse
for 3-5 days before getting better and symptoms can persist for 2-3 weeks.
MEDICINE TREATMENT
 Sodium chloride 0.9%, eye washes or irrigation.
If sodium chloride 0.9% is not available use cooled boiled water/sterile water.

Oxymetazoline 0.025%, ophthalmic drops, instil 1 drop 6 hourly for 7
days.
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EYE DISORDERS
18.1.2 CONJUNCTIVITIS, ALLERGIC
H10.1
DESCRIPTION
Inflammation of the conjunctiva with moderate to severe itching. It may be
associated with hay fever, or other features of atopy. There may be acute
inflammation of the conjunctiva, chronic cobblestone elevations of the tarsal
conjunctiva or chronic thickening and discoloration of the perilimbal
conjunctiva.
MEDICINE TREATMENT
Short-term use
Treatment should be for 5–7 days.
For relief of mild symptoms:
 Oxymetazoline 0.025%, ophthalmic drops, instill 1–2 drops 6 hourly.
Short-term use only.
Long-term use
For control of allergic response in chronic cases:
 Sodium cromoglycate 2%, ophthalmic drops, instill 1–2 drop 6 hourly.
AND
 Cetirizine, oral, 10 mg daily.
REFERRAL
No response to treatment.
18.1.3 CONJUNCTIVITIS, BACTERIAL
H13.1*
DESCRIPTION
Clinical features:
» It may be either unilateral or bilateral.
» There is matting of lashes in the morning with the eyelids stuck shut.
» There is a mucopurulent discharge throughout the day.
» The eyelids may be swollen.
MEDICINE TREATMENT
During the day:
 Chloramphenicol 1%, ophthalmic ointment 8 hourly for 5 days.
i
LoE: III
OR


Fluoroquinolone ophthalmic drops as second-line treatment, e.g.:
Ciprofloxacin 0.3%, ophthalmic drops, instill 1 drop 4 hourly for 2 days.
o Then reduce frequency to 1 drop 6 hourly for 5 days.
OR
2015
18.2
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EYE DISORDERS
Ofloxacin 0.3%, ophthalmic drops, instill 1 drop 4 hourly for 2 days.
o Then reduce frequency to 1 drop 6 hourly for 5 days.
ii
LoE: I
REFERRAL
No response to treatment.
18.2 ENDOPHTHALMITIS, BACTERIAL
H44.0
DESCRIPTION
Infection of the ocular cavity is an emergency as it can cause blindness. This
may occur secondary to bacteraemia (endogenous infection) or, more
commonly, after penetrating ocular injury or surgery.
In patients with endogenous endophthalmitis blood cultures should be done
and the source of infection identified and treated.
In patients with endophthalmitis after penetrating injury/surgery culture
should be done on specimens of aqueous or vitreous humour.
MEDICINE TREATMENT
Refer immediately to an ophthalmologist.
Endogenous endophthalmitis
Specialist initiated, vitrectomy often required:
 Ceftriaxone, IV, 2 g daily for 7 days.
Adjust antibiotics according to culture and sensitivity results.
AND
 Ceftazidime, intravitreal, 2.25 mg.
AND
 Vancomycin, intravitreal, 1 mg.
Administer using separate tuberculin syringes.
iii
LoE:III
iv
LoE:III
Post-surgical endophthalmitis
Specialist initiated, vitrectomy often required:
 Ceftazidime, intravitreal, 2.25 mg.
AND
 Vancomycin, intravitreal, 1 mg.
Administer using separate tuberculin syringes.
In addition, if there is soft tissue involvement or as prophylaxis after a
penetrating eye injury:
 Ciprofloxacin, oral, 750 mg 12 hourly for 7 days.
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EYE DISORDERS
18.3 GLAUCOMA
H40.9
DESCRIPTION
Glaucoma is characterised by damage to the optic nerve with associated
visual field loss, for which raised intra-ocular pressure (IOP) is a primary risk
factor.
Glaucoma is classified as open-angle or angle-closure. Glaucoma may occur
as a primary condition or secondary to other ocular conditions. The condition
is usually bilateral, but may be unilateral or asymmetrical (especially with
secondary causes).
Clinical features
Open-angle glaucoma:
» Mostly asymptomatic.
» History of gradual loss of vision in the affected eye or loss of visual field.
» Often suspected after seeing cupping of optic disc on routine
fundoscopy or finding elevated intra-ocular pressure on screening.
Angle-closure glaucoma:
» Usually presents acutely with sudden onset of severe eye pain and
redness, associated with nausea, vomiting and hemicranial headache.
» Loss of vision in the affected eye.
» Coloured haloes or bright rings around lights.
» Hazy-looking cornea.
» Fixed, semi-dilated pupil.
» Shallow anterior chamber.
» Severely elevated intra-ocular pressure. When measured with finger
palpation, the affected eye feels hard, compared to the other eye.
» If intraocular pressure rises more slowly, the patients may be
asymptomatic with gradual loss of vision.
MEDICINE TREATMENT
Open-angle glaucoma
Refer to an ophthalmology unit for diagnosis and initiation of treatment.
First line
ß-blocker:

Non-selective -blocker, e.g.:

Timolol 0.25%, ophthalmic drops, instill 1 drop 12 hourly.
v
OR
LoE:II
Selective -blocker:

Betaxolol 0.25–0.5%, ophthalmic drops, instill 1 drop 12 hourly.
LoE:III
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18.4
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EYE DISORDERS
Poor response despite adequate adherence:
ADD

Prostaglandin analogues, e.g.:
vi
LoE:II
 Bimatoprost 0.03%, ophthalmic drops, instill 1 drop daily.
o Use as first line if patient has contra-indication to ßblocker.
o Use in place of ß-blocker if patient has intolerable side effects with
ß-blocker or if there is no significant reduction in IOP with other
medicines.
o Use in combination with ß-blocker if there is significant reduction in
IOP with ß-blocker, but patient still has progression of disease or
target IOP is not reached.
Intolerance to prostaglandin analogue, or poor response:

Alpha-agonist, e.g.:
vii
LoE:III

Brimonidine 0.15–0.2%, ophthalmic drops, instill 1 drop
12 hourly.
o Use as second line if patient has allergic reaction to prostaglandin
analogue.
o Use in place of prostaglandin analogue if there is no significant
further reduction in IOP when adding prostaglandin analogue to ßblocker.
o Use in combination with ß-blocker and prostaglandin analogue if
there is significant reduction in IOP with ß-blocker and
prostaglandin analogue, but patient still has progression of disease
or target IOP is not reached.
Failure to respond:
Alternatives in consultation with a specialist:
Parasympathomimetic agent:

Pilocarpine 1%, ophthalmic drops, instill 1 drop 6 hourly.
In severe cases, as a temporary measure before ocular
surgery in consultation with a specialist:
Carbonic anhydrase inhibitors:

Acetazolamide, oral, 250 mg 6 hourly.
LoE:III
viii
LoE:II
Angle-closure glaucoma (acute)
Institute initial therapy and then refer to an ophthalmology unit.
Try to achieve immediate reduction in IOP:

Acetazolamide, oral, 500 mg immediately as a single dose.
o Followed by 250 mg 6 hourly.
AND

Timolol 0.25–0.5%, ophthalmic drops, instill 1 drop 12 hourly.
Also treat patient for associated pain and nausea. See chapter 12:
Anaesthesiology, pain and intensive care.
2015
18.5
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EYE DISORDERS
Where those measures fail, for short-term use only:

Mannitol, IV, 1.5–2 g/kg as a 20% solution over 30–60 minutes.
OR
Glycerol, oral, 1 g/kg of 50% solution as a single dose immediately.
REFERRAL
All to an ophthalmology unit.
18.4 HERPES ZOSTER OPHTHALMICUS
B02.3
DESCRIPTION
Herpes zoster ophthalmicus occurs when the varicella-zoster virus reactivates in
the trigeminal ganglion and passes down the ophthalmic division of the
trigeminal nerve. Patients present with a painful vesicular rash in the trigeminal
V1 area – vesicles on the tip of the nose indicate nasociliary branch involvement,
which increases the risk of ocular involvement. A minority of patients may
develop conjunctivitis, keratitis, uveitis, retinitis and cranial nerve involvement
(oculomotor or optic nerves). Permanent sequelae of ophthalmic zoster infection
may include chronic ocular inflammation, loss of vision, and debilitating postherpetic neuralgia. All patients should be offered HIV testing.
MEDICINE TREATMENT

Aciclovir, oral, 800 mg 4 hourly while awake for 7–10 days.
Note: Treatment should be initiated within the first three days of onset
of symptoms, except in HIV-infected patients who should be treated if
there are active skin lesions.
LoE:III
To reduce the risk of post-herpetic neuralgic pain:

Amitriptyline, oral, 25 mg at night for 3 months.
ix
LoE:II
REFERRAL
»
»
»
»
»
Vesicles on the tip of the nose.
Fluorescein staining of cornea shows corneal/ulceration.
Decreased vision.
Red eye (uveitis or keratitis).
Cranial nerve palsies.
18.5 KERATITIS
18.5.1 KERATITIS, HERPES SIMPLEX
H16.9
DESCRIPTION
Acute unilateral painful red eye with visual blurring and decreased corneal
2015
18.6
CHAPTER 18
EYE DISORDERS
sensation. Characteristic dendritic corneal ulcer seen on staining with
fluorescein.
MEDICINE TREATMENT

Aciclovir 3%, ophthalmic ointment inserted in the lower conjuntival sac
five times per day at 4 hour intervals.
o Continue for 3 days after ulcer has healed.
Note: Topical corticosteroids are contraindicated in the treatment of dendritic
ulcers.
18.5.2 KERATITIS, SUPPURATIVE
H16.0
DESCRIPTION
Painful red eye with corneal lesion that stains with fluorescein and has
creamy white appearance. Contact lenses are a major risk factor, especially
for fungal infections. Have a high index of suspicion for fungal infection if HIV
positive or there is a history of injury to eye with plant matter.
MEDICINE TREATMENT
Empiric therapy until culture results become available:
 Fluoroquinolone ophthalmic drops, e.g.:
 Ciprofloxacin 0.3%, ophthalmic drops, instill 1 drop hourly for 3 days.
o Then reduce frequency to 1 drop 3–4 hourly.
OR
Ofloxacin 0.3%, ophthalmic drops, instill 1 drop hourly for 3 days.
o Then reduce frequency to 1 drop 3–4 hourly.
If fungal infection:
 Natamycin 5%, ophthalmic drops, instill 1 drop 1–2 hourly for 3–4 days.
(Specialist use only).
o Then reduce frequency to 1 drop 3–4 hourly.
o Continue for 14–21 days until resolution of infection.
REFERRAL
»
»
Hypopyon (pus in the anterior chamber)
No facilities for microscopy, culture and sensitivity.
18.6 RETINITIS, HIV CMV
H30.9
DESCRIPTION
Cytomegalovirus (CMV) retinitis is seen in advanced HIV infection, with CD4
3
count < 100 cells/mm . The characteristic retinal appearance is that of
necrosis, i.e. white exudates, and hemorrhages at the edges of the exudates.
2015
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EYE DISORDERS
Visual loss is irreversible – the goal of therapy is to limit further loss.
MEDICINE TREATMENT
Limited CMV retinitis:
 Valganciclovir, oral, 900 mg 12 hourly for the first 3 weeks, then 900 mg
daily until immune recovery (CD4 > 100) and a minimum of 3 months of
x
therapy with valganciclovir (if available).
LoE:I
o Monitor FBC weekly during induction, then monthly as
valganciclovir can cause bone marrow suppression. Avoid concomitant
zidoudine use.
o Initiate ART 2 weeks after starting induction therapy.
If valganciclovir is not available:
 Ganciclovir, intravitreal, 2 mg once a week.
o Once immune function has been restored with antiretroviral therapy
(CD4 >100) and the features of active retinitis has cleared,
maintenance ganciclovir can be stopped but monitor for recurrence.
REFERRAL
To ophthalmologist for confirmation of diagnosis.
18.7 UVEITIS
H20.0
DESCRIPTION
Inflammation of the uveal tract and adjacent structures. The commonest
form is acute anterior uveitis, which presents with pain and photophobia,
variable loss of vision, circumcilliary injection, and a miotic pupil. Chronic
uveitis may lead to cystoid macular oedema with decreased central acuity,
cataract formation and secondary glaucoma. Numerous systemic diseases
can cause uveitis.
MEDICINE TREATMENT

Cycloplegic agent, e.g.:

Homatropine 2 %, ophthalmic drops, instill 1–2 drops 3–4 hourly.
OR
Atropine 1%, ophthalmic drops, instill 1 drop 12 hourly.
AND
Corticosteroids:

Dexamethasone 0.1%, ophthalmic drops, instill 1–2 drops 4–6 hourly.
xi
LoE:III
REFERRAL
All, for management at an ophthalmology unit.
2015
18.8
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EYE DISORDERS
18.8 SURGICAL AND DIAGNOSTIC PRODUCTS
Ocular peri-operative pharmaceutical products

Sodium hyaluronate 10 mg/mL

Acetylcholine chloride (for intra-ocular irrigation)

Sterile intraocular irrigating solution
Ocular diagnostic products

Fluorescein 2 %, ophthalmic drops

Fluorescein ophthalmic strips

Tropicamide 1%, ophthalmic drops

Cyclopentolate 2 mg/mL ophthalmic drops (for cycloplegic refraction)

Cyclopentolate 2mg/mL and phenylephrine 10 mg/mL (for fundoscopic
examination)

Carbopol gel (as coupling liquid for diagnostic contact lenses)
Local anesthetics used on the eye

Oxybuprocaine hydrochloride 0.4%
Preparations for tear deficiency

Hydroxypropylmethylcellulose 0.3–0.5%
18.9 DRY EYE
H04.12
DESCRIPTION
Dry eye occurs when there is inadequate tear volume or function.
The common symptoms include feelings of dryness, grittiness, burning and
foreign body sensation, usually worse during the day. A stringy discharge,
redness and transient blurring of vision are also common.
Allergic conjunctivitis should be excluded.
GENERAL MEASURES
The management of dry eye involves controlling the symptoms, since the
disease is generally not curable.
Patients should be educated to avoid over the counter topical medications,
many of which exacerbate dryness, and control their environmental factors
(e.g. encourage frequent blinking during visually attentive tasks, avoid air
conditioners or heating, use humidifiers).
MEDICINE TREATMENT
Tear substitutes:
 Hydroxypropylmethylcellulose, ophthalmic drops, 1 drop, 6 hourly.
xii
OR
LoE:III
Lanolin, anhydrous liquid, ophthalmic ointment, at night.
xiii
LoE:III
2015
18.9
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EYE DISORDERS
18.10 MEDICAL MANAGEMENT OF EYE INJURY
18.10.1 CHEMICAL BURN
T26.50
This is a medical emergency.
DESCRIPTION
Damage to one or both eyes caused by contact with irritating chemical
substances e.g. alkali or acid.
Presents with:
» pain
» blurred vision
» inability to open eye
» excessive teary and watery eye
GENERAL MEASURES
» Irrigate or wash the eye immediately and continuously with clean water
or sodium chloride 0.9% for at least 20 minutes.
» In severe alkaline burn cases, irrigation should be prolonged further.
MEDICINE TREATMENT
Local anaesthetic if needed:
 Tetracaine 0.5% ophthalmic drops, instil 2 drops in the affected eye.
o Repeat irrigation of eye.
o Evert upper eyelid and remove debris with cotton bud.
xiv
AND
LoE:III
 Chloramphenicol 1%, ophthalmic ointment, applied 6
hourly.
xv
LoE:III
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
xvi
LoE:III
REFERRAL
All cases within 12 hours.
18.10.2 EYE INJURY: BLUNT/PENETRATING/FOREIGN
BODY
S05.90
DESCRIPTION
A foreign body may be embedded in the conjunctivae or cornea or deeper,
causing:
» corneal abrasion/laceration
» disturbance of vision
2015
18.10
CHAPTER 18
EYE DISORDERS
» complaints of foreign body in the eye that may not be visible
» pain
GENERAL MEASURES
Establish the cause, to determine likelihood of penetrating trauma.
If no penetrating injury, irrigate eye with clean water or sodium chloride 0.9%.
Remove any foreign body if visible on sclera or conjunctivae with cotton bud.
If foreign body is not visible, check visual acuity first, before testing with
fluorescein.
Stain with fluorescein to reveal corneal foreign body or complications such
as abrasion.
Cover injured eye with eye pad provided there is no pressure on the eye.
Consider X-ray of orbit to exclude intra-ocular metallic foreign body.
MEDICINE TREATMENT
Corneal abrasion
 Chloramphenicol 1%, ophthalmic ointment applied 8 hourly to the injured eye.
xvii
LoE:III
Deep corneal or scleral injuries
Cover with an eye shield and refer immediately.
If immediate referral is not possible, while awaiting transfer:
 Atropine, 1%, drops, instilled immediately.
AND
 Chloramphenicol 1%, ophthalmic ointment applied
immediately.
xviii
LoE:III
xix
LoE:III
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
xx
LoE:III
REFERRAL
»
»
»
»
»
»
»
2015
Suspicion of open globe or intra-orbital penetration:
- Decreased visual acuity.
- Eccentric or peaked pupil.
- Extrusion of ocular contents or foreign body.
- Circumferential subconjunctival hemorrhage.
Traumatic hyphema (blood in the anterior chamber).
Conjunctival lacerations >1 cm in length that will require suturing.
Foreign bodies that are deeply embedded.
Chemical and thermal burns.
Damage to other structures of the eye, including the eyelid edge.
Limitation of movement of the eye.
18.11
CHAPTER 18
EYE DISORDERS
References:
i
Chloramphenicol 1%, ophthalmic ointment: SAMF, 2014.
ii
Fluoroquinolone ophthalmic drops: Prajna NV, George C, Selvaraj S, Lu KL, McDonnell PJ, Srinivasan M.
Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment
of patients with culture-positive bacterial keratitis. Cornea. 2001 Mar;20(2):175-8.
http://www.ncbi.nlm.nih.gov/pubmed/11248824
Fluoroquinolone ophthalmic drops: Bron AJ, Leber G, Rizk SN, Baig H, Elkington AR, Kirkby GR, Neoh C, Harden
A, Leong T. Ofloxacin compared with chloramphenicol in the management of external ocular infection. Br J Ophthalmol.
1991 Nov;75(11):675-9. PubMed PMID: 1751464. http://www.ncbi.nlm.nih.gov/pubmed/1751464
iii
Ceftazidime, intravitreal: Yonekawa Y, Chan RV, Reddy AK, Pieroni CG, Lee TC, Lee S. Early intravitreal
treatment of endogenous bacterial endophthalmitis. Clin Experiment Ophthalmol.2011 Nov;39(8):771-8.
http://www.ncbi.nlm.nih.gov/pubmed/22050564
Ceftazidime, intravitreal: Okada AA, John RP, Liles WC, D'Amico DJ, Baker AS. Endogenous bacterial
endophthalmitis. Report of a ten-year retrospective study 1994;101(5):832-838.
http://www.ncbi.nlm.nih.gov/pubmed/8190467
iv
Vancomycin, intravitreal: Yonekawa Y, Chan RV, Reddy AK, Pieroni CG, Lee TC, Lee S. Early intravitreal
treatment of endogenous bacterial endophthalmitis. Clin Experiment Ophthalmol.2011 Nov;39(8):771-8.
http://www.ncbi.nlm.nih.gov/pubmed/22050564
Vancomycin, intravitreal: Okada AA, Johnson RP, Liles WC, D'Amico DJ, Baker AS. Endogenous bacterial
endophthalmitis. Report of a ten-year retrospective study. Ophthalmology. 1994 May;101(5):832-8.
http://www.ncbi.nlm.nih.gov/pubmed/8190467
v
Non-selective -blocker: Geyer O, Lazar M, Novack GD, Shen D, Eto CY. Levobunolol compared with timolol: a
four-year study. Br J Ophthalmol. 1988 Dec;72(12):892-6. http://www.ncbi.nlm.nih.gov/pubmed/3067745
Non-selective -blocker: Mills KB, Wright G. A blind randomised cross-over trial comparing metipranolol 0.3%
with timolol 0.25% in open-angle glaucoma: a pilot study. Br J Ophthalmol. 1986 Jan;70(1):39-42.
http://www.ncbi.nlm.nih.gov/pubmed/2868753
vi
Prostaglandin analogues: Parrish RK, Palmberg P, Sheu WP; XLT Study Group. A comparison of latanoprost,
bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, maskedevaluator multicenter study. Am J Ophthalmol. 2003 May;135(5):688-703.
http://www.ncbi.nlm.nih.gov/pubmed/12719078
vii
Alpha-agonist: Schadlu R, Maus TL, Nau CB, Brubaker RF. Comparison of the efficacy of apraclonidine and
brimonidine as aqueous suppressants in humans. Arch Ophthalmol. 1998 Nov;116(11):1441-4.
http://www.ncbi.nlm.nih.gov/pubmed/9823343
viii
Acetazolamide: Maus TL, Larsson LI, McLaren JW, Brubaker RF. Comparison of dorzolamide and
acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol. 1997 Jan;115(1):45-9.
http://www.ncbi.nlm.nih.gov/pubmed/9006424
ix
Amitriptyline: Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized,
double-blind, placebo-controlled trial. J Pain Symptom Manage. 1997 Jun;13(6):327-31.
http://www.ncbi.nlm.nih.gov/pubmed/9204652
x
Valganciclovir: Roche Products (Pty) Ltd. Valcyte 450 film coated tablet®, South African package insert, 27 July
2012.
Valganciclovir: Martin DF, Sierra-Madero J, Walmsley S, Wolitz RA, Macey K, Georgiou P, Robinson CA,
Stempien MJ; Valganciclovir Study Group. A controlled trial of valganciclovir as induction therapy for
cytomegalovirus retinitis. N Engl J Med. 2002 Apr 11;346(15):1119-26. Erratum in: N Engl J Med 2002 Sep
12;347(11):862. http://www.ncbi.nlm.nih.gov/pubmed/11948271
Valganciclovir (3 months duration): Centers for Disease Control and Prevention. Guidelines for prevention and
treatment of opportunistic infections in HIV-Infected adults and adolescents recommendations from CDC, the
National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.
MMWR 2009;58(RR-4):1-216. http://www.cdc.gov/mmwr/pdf/rr/rr5804.pdf
xi
Corticosteroids: McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits
and risks. Drug Saf. 2002;25(1):33-55. http://www.ncbi.nlm.nih.gov/pubmed/11820911
Dexamethasone: McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits
and risks. Drug Saf. 2002;25(1):33-55. http://www.ncbi.nlm.nih.gov/pubmed/11820911
xii
Hydroxypropylmethylcellulose, ophthalmic drops: SAMF, 2014
xiii
Lanolin, anhydrous liquid, ophthalmic ointment: SAMF, 2014
xiv
Tetracaine 0.5% ophthalmic drops: Primary Healthcare STGs and EML. http://www.health.gov.za
xv
Chloramphenicol 1%, ophthalmic ointment: Primary Healthcare STGs and EML. http://www.health.gov.za
xvi
Paracetamol, oral: Primary Healthcare STGs and EML. http://www.health.gov.za
xvii
Chloramphenicol 1%, ophthalmic ointment:: Primary Healthcare STGs and EML. http://www.health.gov.za
xviii
Atropine, 1%, drops: Primary Healthcare STGs and EML. http://www.health.gov.za
xix
Chloramphenicol 1%, ophthalmic ointment: Primary Healthcare STGs and EML. http://www.health.gov.za
xx
Paracetamol, oral: Primary Healthcare STGs and EML. http://www.health.gov.za
2015
18.12
CHAPTER 19
POISONING
POISON CENTRES
POISON INFORMATION CENTRES
Western Cape:
24 hours, every
day for poisons
queries
Poison Information Helpline of the
Western Cape
0861 555 777
Tygerberg Poison Information
Centre
0861 555 777
Email: [email protected]
www.sun.ac.za/poisoncentre
Red Cross War Memorial Children’s
Hospital Poisons Information
Service
Free State:
(operates until
21:00)
University of the Free State Poison
Control and Medicine Information
Centre
0861 555 777
082 491 0160
Telephone numbers tested 25 February 2016
Poison information can be accessed through: https://www.afritox.co.za/
ENVENOMATION
19.1 INSECT BITES AND STINGS
T63.4
DESCRIPTION
Insect bites and stings usually cause local effects only. Systemic effects are
rare. Local inflammatory or systemic/immunological forms of toxicity are
encountered occasionally, which may vary between minor local reactions
and acute anaphylaxis.
Multiple bee stings may require ICU care.
2015
19.1
CHAPTER 19
POISONING
GENERAL MEASURES
Severe allergic reactions may be delayed.
Beware of premature discharge from the healthcare facility.
MEDICINE TREATMENT
Anaphylaxis: See section 20.1.2: Anaphylaxis/Anaphylactic Shock.
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
LoE:III
19.2 SNAKEBITES
T63.0
DESCRIPTION
As the majority of snakes are not identified in snakebite victims, the table below
illustrates the syndromic management of three main envenomation syndromes
namely: cytotoxic, neurotoxic and haemotoxic.
To view pictures for identification of snakes click on following hyperlink:
http://www.cmej.org.za/index.php/cmej/article/view/2546/2581
Signs of systemic poisoning:
» Muscle weakness and/or difficulty in breathing.
» Difficulty in swallowing or speaking with drooling.
» Weakness.
» Double vision and drooping eyelids.
» Spreading of local tissue damage.
» Swelling of a hand or foot within 1 hour of a bite (the majority of bites
occur on the hands or feet).
» Swelling extending to the elbows or knees within 4 hours of a bite.
» Swelling of the groin or chest at any time or if actively advancing.
» Significant swelling of head or neck.
2015
19.2
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POISONING
Venom type
Cytotoxic
Neurotoxic
Mixed
cytotoxic and
neurotoxic
Snake species
Puff adder,
Gaboon adder,
spitting cobra
(Mozambique,
black-necked,
zebra), stiletto
snake, night
adders, horned
adders
Black and
green mamba,
non-spitting
cobra (e.g.
snouted, Cape,
forest,
Egyptian,
Anchieta)
Rinkhals, Berg Boomslang,
adder,
vine snakes.
Peringuey’s
adder, desert
mountain
adder, garter
snakes, Shieldnose snake.
Predominant
clinical
presentation
» Painful,
» Respiratory
» Combined
progressive
swelling
distress,
» Progressive
weakness
» Cranial nerve
palsies
Antivenom
availability.
See indications
for antivenom
treatment
Polyvalent
antivenom for
Puff adder,
Gaboon adder
and spitting
cobras only
Polyvalent
antivenom for
all species
painful
progressive
swelling and
progressive
weakness or
respiratory
failure
Polyvalent
antivenom for
rinkhals only
Haemotoxic
» Bleeding
(Presents late
>24 hours post
bite)
Boomslang
antivenom for
confirmed
boomslang
bites only.
GENERAL MEASURES
Supportive and symptomatic treatment is essential for survival.
Mechanical ventilation may be needed in some cases.
MEDICINE TREATMENT
Cleanse wound:

Chlorhexidine 0.05% in water.
Antibiotics are seldom needed, except for secondary infection:

Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 5 days.
i
LoE:III
Immunisation, primary or booster:

Tetanus toxoid vaccine, IM, 0.5 mL immediately.
In unimmunised or partially immunised patients:

Tetanus immunoglobulin, human, IM, 250 units immediately.
2015
19.3
CHAPTER 19
POISONING
Analgesia
For mild pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
OR
For severe pain:
ADD
 Opioids, e.g.:
o Morphine, IV, to a total maximum dose of 10 mg (See Appendix II,
for individual dosing and monitoring for response and toxicity).
o Opioids should be used cautiously in neurotoxic snakebite.
LoE:III
Note: The use of an NSAID is not recommended due to the antiplatelet
effect and the potential danger of renal failure in a hypotensive patient.
ii
LoE:III
Polyvalent antivenom
Obtainable from South African Vaccine Producers (tel: +2711 386-6063/2/00).
See package insert for full details.
It is ineffective against the venom of:
» night and berg adder and other minor adders,
» boomslang, and
» vine and twig snakes.
Caution
Never administer antivenom without being fully prepared to manage acute
anaphylaxis.
Note:
» In most cases patients do not need and should not be given antivenom.
iii
LoE:III
» Adverse reactions to antivenom are common and may be severe.
» The dose of antivenom is the same for adults and children.
» Monitor for any deterioration in respiratory function as patients may need
ventilation whether or not polyvalent antivenom has been given.
LoE:III
Indications for polyvalent antivenom:
» Any sign of neurotoxicity.
» All patients with confirmed mamba bites should receive antivenom, even
before the onset of symptoms and signs.
» Patients with confirmed puff adder or Gaboon adder bites should receive
antivenom at the onset of any symptoms and signs of cytotoxicity.
2015
19.4
CHAPTER 19
»
POISONING
Extensive swelling or cardiovascular abnormalities despite unidentified
snake.
Premedication for antivenom:

Adrenaline (epinephrine), SC, 0.25 mL of 1:1000 solution.
(Contraindicated in patients with IHD, stroke, uncontrolled hypertension
and tachyarrhythmia).
iv
LoE:I

Polyvalent snake antivenom, slow IV infusion.
o 1 ampoule contains 10 mL antivenom.
o Dilute in sodium chloride 0.9%.
o Administer slowly, IV, for the first 30 minutes, as most allergic
reactions will occur within this period.
o Increase the flow rate gradually to complete the infusion within 1 hour.
o Repeat if there is no clinical improvement (e.g. improvement and
recovery of muscle paralysis or improvement of neurotoxic signs)
after the infusion.
o Antivenom may be administered up to 24-48 hours or later, in
serious envenomation.
Snakebite
Cytotoxic snakebite
Cytotoxic snakebite of
head and neck
Neurotoxic snakebite
Dose of polyvalent snake antivenom
o 50mL (5 ampoules).
o Dilute in ±100–200 mL sodium chloride 0.9%.
o If clinically indicated, administer a second
dose.
o 100 mL (10 ampoules) to 200 mL (20
ampoules).
o Dilute in ±100–200 mL sodium chloride 0.9%.
o If clinically indicated, administer a second
dose.
o 100 mL (10 ampoules) and up to 200 mL (20
ampoules).
o Dilute in ±100–200 mL sodium chloride 0.9%.
For black mamba snakebites:
o 200 mL (20 ampoules).
o Dilute in ±100–200 mL sodium chloride 0.9%.
o If clinically indicated, administer a second
dose.
v
LoE:III
2015
19.5
CHAPTER 19
POISONING
19.2.1 BOOMSLANG SNAKE BITE
T63.0
DESCRIPTION
Consumptive coagulopathy usually sets in within 6–36 hours after the bite
with hypofibrinogenaemia and bleeding.
In suspected boomslang bite a whole blood clotting time is a useful bedside
test, especially in rural areas. Place 5 mL of blood in a dry glass test tube
and leave at room temperature for 20 minutes. Normal clotting time varies
from 5–20 minutes. It is important to follow these over a few days.
Other investigations include FBC, activated PTT, prothrombin time (INR),
fibrinogen, D-dimer and monomers.
Management includes fluid replacement therapy with electrolyte solutions and
blood components (packed cells, plasma). The haemostatic effects of
boomslang envenomation are rapidly reversed on administration of the specific
boomslang antivenom.
Note: Polyvalent antivenom is not effective in boomslang bite.
Boomslang antivenom
Obtainable from South African Vaccine Producers (tel: +2711 386-6063/2/00).
See full details in the package insert.
Caution
Never administer antivenom without being fully prepared to manage acute
anaphylaxis.

Boomslang antivenom, slow IV infusion, 20 mL diluted in 50–100 mL
sodium chloride 0.9% or dextrose 5%, administered over 5–10 minutes.
o Re-evaluate at 2 hours and if evidence of ongoing coagulopathy a
follow-up dose of 10 mL may be considered.
vi
LoE:III
19.2.2 VENOM IN THE EYE
T63.094
DESCRIPTION
Direct or indirect snake venom exposure to the eye, particularly from various
species of spitting cobras, can cause chemical injury with varying clinical
presentations ranging from periocular swelling and mild conjunctival and corneal
inflammation to frank corneal ulceration and perforation with eventual blindness.
GENERAL MEASURES

Instil local anaesthetic and promptly perform copious irrigation to dilute
or
2015
19.6
CHAPTER 19

POISONING
remove the toxin with sodium chloride, 0.9%.
Apply chloramphenicol ointment and cover the affected
eye with an eye patch.
LoE:III
REFERAL
Refer all patients to an ophthalmologist.
19.3 SCORPION ENVENOMATION
T63.2
DESCRIPTION
Poisonous scorpions in Southern Africa are of the genus Parabuthus (P.
granulatus and P. transvaalicus). These are large scorpions measuring 7–15
cm in length.
Features useful in their identification are a relatively large tail and small
pincers. The venom typically causes immediate and severe local pain,
followed by systemic neurotoxic symptoms and signs within 1–4 hours, but
symptoms can be delayed up to 8 hours.
To view pictures for identification of scorpions click on following hyperlink:
http://www.cmej.org.za/index.php/cmej/article/view/2545/2580
Clinical features of scorpion stings include:
» Immediate and excruciating pain
» general paraesthesias and hyperaesthesia,
» tremors and involuntary movements
» muscle pain, cramps, and weakness,
» excessive sympathetic stimulation,
» dysphagia,
» dysarthria, and
» increased salivation and loss of pharyngeal reflexes with possible
respiratory impairment/failure.
GENERAL MEASURES
Observe all cases for at least 12 hours.
Monitor respiratory function.
Ventilatory support may be required.
MEDICINE TREATMENT
Antivenom therapy is recommended only in cases presenting with systemic
neurotoxic effects.

Scorpion antivenom, IV infusion, 10 mL diluted in 100 mL sodium
chloride 0.9% or dextrose 5%, administered over 10 minutes.
LoE:III
Immunisation, primary or booster:

Tetanus toxoid vaccine, IM, 0.5 mL immediately.
2015
19.7
CHAPTER 19
POISONING
In unimmunised or partially immunised patients:

Tetanus immunoglobulin, human, IM, 250 units immediately.
Analgesia
For pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
vii
LoE:III
Severe local pain:

Lidocaine 1–2%, 2 mL: infiltrate affected area as a local anaesthetic.
viii
LoE:III
Opiates are not effective and increase the risk of respiratory
depression.
ix
LoE:III
Severe muscle pain and cramps:

Calcium gluconate 10%, bolus IV infusion, 10 mL over 10 minutes.
o Repeat if needed.
19.4 SPIDER ENVENOMATION
T63.3
DESCRIPTION
Local venomous spiders are divided into cytotoxic and neurotoxic groups.
To view pictures for identification of spiders click on following hyperlink:
http://www.cmej.org.za/index.php/cmej/article/view/2547/2582
Cytotoxic spider group
The cytotoxic group includes sac, violin and crab spiders.
May present with significant bite site necrosis, which may need surgical
debriding. Bites may take weeks/months to heal.
Note: Antibiotics are reserved for secondary infection.
Neurotoxic spider group
The neurotoxic group is represented by the black and brown widow (also
known as button) spiders (genus Latrodectus). Black widow spiders are
more venomous than brown widow spiders.
Features useful in the identification of the black widow spider are:
» Black or dark brown colour.
» Variable red markings on the dorsal aspect of the abdomen, which
diminish with age. It has no ventral markings.
2015
19.8
CHAPTER 19
POISONING
Features of brown widow spider:
» Typical orange coloured hourglass shaped marking on the ventral
surface of the abdomen.
Envenomation may cause:
» Local burning pain and painful, tender regional lymph nodes.
» Severe general muscle pain and cramps especially of the large girdle
muscles.
» Muscle rigidity.
» Feeling of tightness of the chest.
» Board-like rigidity of a non-tender abdomen.
» Profuse sweating may be prominent.
» General muscle pain which lasts for days to a week if antivenom is not
given.
GENERAL MEASURES
Observe all cases for at least 24 hours.
MEDICINE TREATMENT

Spider antivenom, IV infusion, 5–10 mL diluted in 50–100 mL sodium
chloride 0.9% or dextrose 5%, administered over 5–10 minutes.
x
Note: Antivenom is only indicated for systemic symptoms in
LoE:III
patients with black widow spider bites.
Caution
Never administer antivenom without being fully prepared to manage acute
anaphylaxis.
Severe muscle pain and cramps:

Calcium gluconate 10%, bolus IV infusion, 10 mL over 10 minutes.
o Repeat if needed.
Immunisation, primary or booster:

Tetanus toxoid vaccine, IM, 0.5 mL immediately.
In unimmunised or partially immunised patients:

Tetanus immunoglobulin, human, IM, 250 units immediately.
Analgesia
For mild pain:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4g in 24 hours.
2015
19.9
CHAPTER 19
POISONING
For secondary infection:
See section 4.2: Cellulitis and Erysipelas.
EXPOSURE TO POISONOUS SUBSTANCES
GENERAL MEASURES
Limit further exposure to poison and protect healthcare workers.
It is very important to ascertain if a TOXIC DOSE has been taken BEFORE
instituting any potentially harmful decontamination procedures in an
asymptomatic patient.
Take a complete and accurate history, ascertain all relevant facts and do a
complete clinical examination. A high index of suspicion is important.
Obtain a collateral history, especially for patients with impaired
consciousness. A special effort should be made to obtain tablets, packets,
containers, etc. to identify agents involved.
In case of skin exposure, wash body and remove clothes. Showering may be
useful. Remove eye contaminants, especially alkalis, acids and other
irritants, by continuous irrigation of the eye for 15–20 minutes.
Gastric lavage is seldom indicated.
xi
LoE:I
Gastric lavage is ineffective unless done within an hour of ingestion (if
substances are known to delay gastric emptying, consult with poisons
centre). It is contra-indicated after ingestion of corrosive substances and
volatile hydrocarbons such as paraffin. In patients with reduced
consciousness it should be done only if the airway is protected.
Limit toxicology investigations to those that may influence/alter
management. It is important to note the time after ingestion when blood
was taken in order to correctly interpret results (e.g. paracetamol, iron
ingestion).
LoE:III
Maintain and monitor basic clinical parameters, i.e.:
» pulse rate,
» blood pressure,
» hydration,
» ventilation,
» patent airway and oxygenation, and
» control seizures and prevent physical injury in the restless - avoid
excessive sedation.
2015
19.10
CHAPTER 19
POISONING
INITIATION OF TREATMENT
Reduce absorption
Activated charcoal may reduce systemic absorption of a variety of poisonous
substances. The greatest benefit is achieved if activated charcoal is given
within one hour after ingestion of poisonous substances. Repeated doses of
activated charcoal (i.e. 50 g every 4 hours) are effective when managing
carbamazepine, dapsone, phenobarbitone, quinine or theophylline overdose.
xii
LoE:III
Activated charcoal is of no value after ingestion of the
following:
» strong acids or bases,
» other corrosives substances e.g. household detergents,
» iron, lead, mercury, arsenic,
» petroleum products (e.g. paraffin or petrol), and
» ethylene glycol, methanol, ethanol.

Charcoal, activated, oral, 50 g (equivalent to 36 level medicine
measures) diluted in 300 mL water.
o When mixing, add a small amount of water to charcoal in a
container.
o Cap and shake container to make a slurry and then dilute further.
LoE:III
Alkalinisation of urine (e.g. severe salicylate poisoning)
Caution
This is a high risk procedure and should only be performed in consultation
with a specialist.
Haemodialysis
Patients with symptomatically severe poisoning due to salicylates, lithium,
ethylene glycol, methanol, ethanol and theophylline may benefit from dialysis.
Refer patient to a hospital with dialysis facilities.
REFERRAL
»
»
»
»
Severely ill patient for ventilatory/circulatory support.
Relevant diagnostic testing not available, e.g. paracetamol levels.
Relevant medication/antidote not available.
Dialysis/haemoperfusion required.
2015
19.11
CHAPTER 19
POISONING
19.5 ANALGESIC POISONING
19.5.1 PARACETAMOL POISONING
T39.1
DESCRIPTION
Liver damage, due to the depletion of glutathione and accumulation of toxic
metabolites, can occur in any individual with paracetamol overdose. High
risk patients (see below) may experience toxicity at lower ingested doses.
Clinical features
Within 24 hours after overdose
Gastrointestinal symptoms (anorexia, nausea, vomiting, malaise)
predominate in the first 0.5-24 hours. During the next 24-48 hours the
patients may become asymptomatic. Those with normal or only slightly
raised plasma paracetamol levels usually continue to full recovery. In
patients with significantly raised plasma levels this "recovery" may be
spurious and early hepatic toxicity (right upper quadrant abdominal pain and
tenderness, elevated bilirubin, raised liver enzymes, coagulation defects)
may manifest from 20-24 hours, peaking in severity at about 72-96 hours.
This may be followed by full recovery by 5-7 days, or death from hepatic
failure, or less commonly, renal failure.
High risk patients include:
» Chronic alcoholism.
» Chronic liver disease.
» Use of enzyme-inducing medicines (e.g. carbamazepine, phenytoin,
efavirenz, phenobarbitone, rifampicin etc.).
» Depletion of glutathione resources (e.g. malnutrition, starvation, AIDS,
chronic illness, eating disorders etc.).
» Patients with recent illness, dehydration.
Treatment:
The treatment of paracetamol overdose depends on the dose ingested and
the time of presentation since ingestion. A serum paracetamol level is
plotted on the nomogram to assess the risk for hepatotoxicity. Values which
appear above the treatment line require the antidote N-acetylcysteine (NAC).
Acute single ingestion <8 hours post-ingestion:
Toxic dose defined as >150 mg/kg or 7.5 g (whichever is less).
Give activated charcoal if the patient presents within 1-2 hours of ingestion
Perform a serum paracetamol level after 4 hours post-ingestion
If serum paracetamol level results will not be available before 8 hours postingestion, and the patient has taken a toxic dose, do not delay initiation of
NAC. It can always be stopped if the serum level plotted on the nomogram
does not indicate its use.
2015
19.12
CHAPTER 19
POISONING
Acute single ingestion >8 hours post-ingestion:
Toxic dose defined as >150 mg/kg or 7.5 g (whichever is less)
Start NAC infusion if a toxic dose has been ingested or the patient shows
clinical signs of toxicity.
Perform serum paracetamol level, INR and ALT.
Indications for continuing NAC infusion:
» serum paracetamol level above the treatment line on the nomogram
(Note the lower treatment line for high risk patients)
» serum paracetamol level under the treatment line and abnormal ALT
» more than 24 hours post-ingestion, measurable paracetamol level
and/or ALT abnormal
Acute single ingestion with unknown time of ingestion
Manage as for > 8 hours post-ingestion.
Paracetamol treatment nomogram
Source: Daly FF, Fountain JS, Murray L, Graudins A, Buckley NA; Panel of Australian and New
Zealand clinical toxicologists. Guidelines for the management of paracetamol poisoning in
Australia and New Zealand -explanation and elaboration. A consensus statement from clinical
toxicologists consulting to the Australasian poisons information centres. Med J Aust. 2008 Mar
3;188(5):296-301.
xiii
LoE:III
MEDICINE TREATMENT
N-acetylcysteine is the antidote of choice and should be given intravenously.
Although it is more effective when given within 8 hours of ingestion of
paracetamol, there may be benefit even if liver failure has developed.
2015
19.13
CHAPTER 19
POISONING
Histamine may be released, which mimics an allergic reaction. If this occurs
and the patient is stable, infusion may continue at a slower rate under
antihistamine cover. In the presence of bronchospasm, stop the infusion.

N-acetylcysteine, IV:
o Initial infusion: 150 mg/kg diluted in 200 mL 5% dextrose given over
60 minutes.
o Second infusion: 50mg/kg in 500mL 5% dextrose over 4 hours.
o Third infusion: 100mg/kg in 1000mL 5% dextrose over 16 hours.
o Any further N-acetylcysteine is given according to the third infusion
regimen.
LoE:III
Further investigations and referral
Blood tests such as renal function, clotting profile, serum glucose and
acid/base status should only be done where clinically indicated.
Patients who develop liver failure should be referred for further management
and/or possible transplant.
Note: Avoid giving activated charcoal if giving N-acetylcysteine orally as it
will reduce the systemic absorption and thus negate the effect of oral Nacetylcysteine.
19.5.2 SALICYLATE POISONING
T39.0
DESCRIPTION
Mild to moderate toxicity:
» Nausea, vomiting, tinnitus, tachypnea and respiratoric alkalosis
Severe toxicity:
» Metabolic acidosis, fever, altered mental status, seizures, coma, noncardiogenic pulmonary oedema.
GENERAL MEASURES
Consider ICU admission for pulmonary and/or cerebral oedema.
MEDICINE TREATMENT

»
»
Prevent absorption with activated charcoal and whole bowel irrigation of
xiv
slow release or enteric coated formulations.
LoE:III
Assess severity with history, clinical examination and
salicylate levels if possible.
Note: Wintergreen oils/ ointments contain 98 % methyl salicylate.
Treat acidosis and enhance renal excretion (intravenous sodium
bicarbonate and urinary alkalinisation, blood pH < 7.5 and urine pH 7.5–
8.5) in consultation with specialist advice.
LoE:III
2015
19.14
CHAPTER 19
POISONING
REFERRAL
Where acidosis does not respond rapidly to sodium bicarbonate, consider
haemodialysis.
19.5.3. OPIOID POISONING
T40
DESCRIPTION
Patients present with respiratory depression and constricted pupils. Noncardiogenic pulmonary oedema may be present.
GENERAL MEASURES
Supportive management aimed at maintaining cardiorespiratory function.
MEDICINE TREATMENT

Naloxone, IV, 0.4 mg immediately, in patients with respiratory
depression.
o Effectiveness is limited by short half-life of ± 1 hour and repeated
doses may be needed at 2 to 3 minute intervals.
o If there is no response after 10 mg of naloxone is administered, the
diagnosis of opioid-induced or partial opioid-induced toxicity should
be questioned.
o Consider intramuscular or subcutaneous administration, if the
intravenous route is not available.
o Careful monitoring of patient where naloxone was administered is
important until patient is fully awake or no longer naloxone dependant.
xv
LoE:III
19.6 ANTIDEPRESSANTS
19.6.1. TRICYCLIC ANTIDEPRESSANT POISONING
T43.0
DESCRIPTION
Patients may have:
Mild to moderate poisoning:
»
Sedation.
»
» Hallucinations.
» Anticholinergic effects:
delirium,
dilated pupils,
dry mouth.
2015
Tachycardia.
blurred vision,
urinary retention, or
19.15
CHAPTER 19
Severe Poisoning:
» Acidaemia.
» Coma.
» Hypotension.
POISONING
»
»
»
Seizures.
Pulmonary oedema.
QRS prolongation, ventricular dysrhytmias.
GENERAL MEASURES
Do a baseline ECG in all patients.
Patients who are symptomatic 6 hours after ingestion or if there are any
abnormalities on ECG:
» Admit and monitor (ECG and blood gases)
» Discharge the patient only when
- asymptomatic, or
- symptomatic, but ECG has normalised for 24 hours.
» ICU admission for ventilatory/circulatory support, when indicated.
» Manage gastrointestinal ileus and urinary retention appropriately by
giving patients nil per mouth and inserting a urinary catheter.
MEDICINE TREATMENT

Activated charcoal, single dose.
Serum alkalinisation for all patients with dysrhytmias or QRS widening >100
msec or hypotension:

Sodium bicarbonate, bolus doses, to achieve a pH of 7.45–7.55.
(Specialist consultation).
LoE:III
For torsades de pointes not responding to alkalinisation:
ADD
 Magnesium sulphate, IV, 2 g administered over 5–10 minutes.
If recurrent episodes after initial dose of magnesium sulphate:
 Magnesium sulphate, IV, 2 g administered over 24 hours.
LoE:III
For seizures or if sedation is required for restlessness:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
Intravenous fluids
Reverse circulatory shock, if present.
In severe cases, provide inotropic support and monitor response.
Note: The use of flumazenil is not recommended in any patient with possible
tricyclic antidepressant poisoning as it increases the risk of convulsions and
dysrhythmias.
xvi
LoE:I
2015
19.16
CHAPTER 19
POISONING
19.7 IRON POISONING
T45.4
DESCRIPTION
Iron is a commonly prescribed drug, especially in pregnancy, and causes
initial gastrointestinal toxicity.
Patients may have a stage of “apparent recovery” 6–36 hours post-ingestion.
This should not be confused with true recovery as patients may
subsequently deteriorate.
Significant exposure may be associated with:
» severe vomiting and diarrhoea
» gastrointestinal haemorrhage
» metabolic acidosis,
» hypotension,
» CNS side effects,
» renal failure, and
» hepatitis.
GENERAL MEASURES
Gastrointestinal decontamination by whole bowel irrigation is recommended,
if > 40 mg/kg elemental iron has been ingested or if the amount is unknown.
Ferrous salt
Amount
Elemental iron
Ferrous sulphate
300 mg
60 mg
Ferrous gluconate
300 mg
35 mg
Ferrous fumarate
200 mg
65 mg
Activated charcoal does not bind iron and is not indicated in isolated iron
overdose.
Iron concentration should be measured 4–6 hours after ingestion and
repeated every 6 hours until peak.
Give intravenous fluids for hypotension.
MEDICINE TREATMENT
Chelation therapy
Patients with serum iron levels < 54 micromol/L and absence of symptoms >
6 hours after overdose do not require chelation therapy.
Desferrioxamine (deferoxamine) may be used for the following indications (in
consultation with a poison centre):
» Severe symptoms (altered mental status, hemodynamic instability,
persistent vomiting and or diarrhoea).
» Metabolic acidosis.
» Peak serum iron concentration > 90 micromol/L.

Desferrioxamine (deferoxamine), IV infusion, 15 mg/kg/hour.
o The infusion rate can be titrated in consultation with a specialist.
o Note: Prolonged use > 24 hours of high doses is associated with
xvii
acute lung injury and should be avoided.
LoE:III
2015
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POISONING
Desferrioxamine can be used in pregnant women.
xviii
Consider exchange transfusion in patients who deteriorate
despite supportive care and chelation therapy.
LoE:III
Haemodialysis may be needed to remove desferrioxamine-iron complexes in
patients with renal insufficiency.
19.8 THEOPHYLLINE POISONING
T48.6
DESCRIPTION
Patients present with:
» tachycardia and tachyarrhythmias,
» vomiting
» agitation
» seizures
»
»
»
»
nausea
abdominal pain
restlessness
profound hypokalaemia
GENERAL MEASURES
Monitor ECG and treat dysrhythmias.
Monitor and correct fluid status and electrolyte abnormalities.
Monitor theophylline concentrations. Levels may continue to rise up to 24
hours after ingestion of modified release preparations.
MEDICINE TREATMENT

Activated charcoal.
o Give multiple doses activate charcoal (25 g every 4 hours) to
xix
increase elimination.
LoE:III
Correct hypokalaemia:
 Potassium chloride, IV, maximal dose 40 mmol/L and maximal rate 20
mmol/hour.
For seizures:
 Diazepam IV, 10 mg as a single dose.
o Repeat after 5–10 minutes if necessary.
o If seizure persists, consult a specialist.
REFERRAL
In patients with symptoms of severe overdose, refer for dialysis.
2015
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POISONING
19.9 SEDATIVE HYPNOTIC POISONING
19.9.1 BENZODIAZEPINE POISONING
T42.4
DESCRIPTION
Patients present with depressed levels of consciousness, confusion, ataxia
and dysarthria. Benzodiazepines are unlikely to cause significant respiratory
suppression unless co-ingested with alcohol or other CNS depressants.
However, in the elderly, the danger of respiratory depression with overdose
exists.
Management is supportive and ventilation may be required.
Note: The use of flumazenil is not recommended in any patient with possible
benzodiazepine poisoning as it increases the risk of convulsions and
dysrhythmias.
xx
LoE:I
19.9.2 LITHIUM POISONING
T43.9
DESCRIPTION
Lithium toxicity mostly occurs with chronic therapy and may be precipitated
by decreased excretion of the medicine due to renal dysfunction, diuresis,
dehydration or drug-drug interactions (e.g. NSAIDs, diuretics, ACE-inhibitors
and ARBs).
Signs and symptoms include:
» nausea and vomiting
» diarrhoea
» nystagmus
» ataxia
» tremors
» dehydration
» Other CNS symptoms: hyperreflexia, cogwheel rigidity, ataxia, agitations,
confusion and lethargy
In severe toxicity:
» decreased level of consciousness
» confusion,
» dysrhythmias
»
»
restlessness,
seizures,
GENERAL MEASURES
Whole bowel irrigations with polyethylene glycol considered with large
ingestion or sustained-release products.
xxi
LoE:II
Monitor:
» Vitals signs, mental status and urine output
» Do serial lithium levels until peaked and declined.
» Electrolytes and renal function.
2015
19.19
CHAPTER 19
»
»
»
POISONING
Fluid status and administer sodium chloride 0.9 % to obtain normal urine
flow but prevent hypernatremia.
Cardiac function and treat dysrhythmias (see chapter 3: Cardiovascular
system).
Thyroid function.
MEDICINE TREATMENT
Correct hypokalaemia actively:
 Potassium chloride, IV, maximal dose 40 mmol/L and maximal rate 20
mmol/hour.
For seizures:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
Haemodialysis
Indicated in severe lithium poisoning. Discuss with a specialist.
LoE:III
19.10 ISONIAZID POISONING
T37.1
DESCRIPTION
Acute toxicity: can present with the classic triad of seizures, metabolic
acidosis and coma.
Seizures are generalised tonic-clonic and often refractory to standard
anticonvulsant therapy.
GENERAL MEASURES
Supportive management aimed at preventing and managing complications.
Treat hyperthermia.
MEDICINE TREATMENT

Pyridoxine, oral,
o 1 g for every gram of isoniazid ingested, or
o 5 g for unknown amount ingested.
xxii
LoE:III
19.11 CALCIUM CHANNEL BLOCKER POISONING
T46.1
GENERAL MEASURES
Monitor vital signs, ECG and blood glucose.
Hyperglycemia in non-diabetic patients with a history of possible CCB
ingestion may assist with diagnosis.
Treat symptomatic patients in consultation with a specialist.
2015
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CHAPTER 19
POISONING
MEDICINE TREATMENT
Treat hypotension:

Sodium chloride, IV, 0.9%.
xxiii
Treat bradycardia:

Atropine 0.5–1 mg every 2–3 minutes to a maximum of 3 mg.
LoE:III
xxiv
LoE:III
If not effectively controlled add:

Calcium gluconate 10%, IV, 10 mL given over 15–30 minutes, with ECG
monitoring.
o This may be repeated.
xxv
LoE:III
Use vasopressors as needed.
In patients with resistant hypotension and bradycardia and glucose < 8
mmol/L:

Dextrose 50%, IV, 50 mL.
Followed by:

Short acting insulin, IV, 1 unit/kg.
o
Followed by 0.5 unit/kg/hour.
o Titrate dose up until hypotension is corrected
o Monitor and correct potassium and glucose.
xxvi
LoE:III
19.12 COTRIMOXAZOLE POISONING
T37.0
DESCRIPTION
Symptoms of toxicity include nausea and vomiting, dizziness, headache and
neurological symptoms (such as drowsiness, confusion and mental
depression). Other signs include: bone marrow depression, haematuria and
renal insufficiency.
GENERAL MEASURES
Treatment is symptomatic and supportive.
Monitor FBC, electrolytes, glucose, hepatic and renal function in
symptomatic patients.
19.13 ANTIRETROVIRAL AGENTS POISONING
T37.5
DESCRIPTION
Limited data is available regarding overdose of these medicines.
Toxicological effects are generally extensions of adverse effects.
GENERAL MEASURES
Monitor FBC, serum electrolytes, renal and liver function.
2015
19.21
CHAPTER 19
POISONING
Monitor serum lipase in patients with abdominal pain.
Lactic acid and serum pH should be monitored in acidotic patients.
TREATMENT
There are no specific antidotes.
Treatment is symptomatic and supportive.
19.14 ILLICIT DRUGS
19.14.1 COCAINE POISONING
T40.5
DESCRIPTION
Cocaine may be absorbed through any mucous membrane, smoked or injected
intravenously.
Patients may present with one or more of the following:
» acute myocardial infarction » seizures
» cardiac dysrhythmias
» alterations in mood and confusion
» tachycardia
» hypertension
»
pulmonary oedema
» stroke
» intestinal ischaemia
» rhabdomyolysis with acute renal failure
GENERAL MEASURES
Supportive management aimed at preventing and managing complications.
Cool patients with hyperthermia.
Abdominal X-rays may show packages of cocaine. In these patients,
conservative management is recommended.
Activated charcoal and whole bowel irrigation may decrease absorption.
Surgery is reserved for those who develop obstruction or perforation.
Raised serum creatinine kinase may indicate rhabdomyolysis or myocardial
infarction.
Note: Lidocaine may precipitate seizures.
ß–blockers should not be used.
MEDICINE TREATMENT
For sedation or seizures:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
Status epilepticus:
See section 14.3.1: Status Epilepticus.
2015
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CHAPTER 19
POISONING
Psychosis or delirium with severe agitation:

Benzodiazepines:

Lorazepam, IM, 4 mg, immediately.
OR
Midazolam, IM, 15 mg immediately.
OR
Clonazepam, IM, 2 mg, immediately.
OR
Diazepam, IV, 10 mg.
o Repeat after 30–60 minutes if needed.
OR
Haloperidol, IM, 5 mg, immediately.
AND
Promethazine, deep IM, 25–50 mg.
o In the elderly 25 mg.
Repeat after 30–60 minutes if needed.
If haloperidol is unavailable, use chlorpromazine without promethazine.

Chlorpromazine, deep IM, 25–50 mg.
o May be repeated as necessary 4 times in 24 hours.
xxvii
LoE:III
Severe hypertension:
See section 3.6.1: Hypertension, severe.
19.14.2 POISONING WITH AMPHETAMINE DERIVATIVES
T43.6
DESCRIPTION
These include:
» “Ecstasy”: 3,4-methylenedioxymethamphetamine (MDMA).
» “Ice” and “Eve”: 3,4-methylenedioxy-N-ethylamphetamine (MDEA).
» “Tik”: Methamphetamine.
Drug effects are due to the increased release of noradrenaline, dopamine
and serotonin in the CNS. Patients present with:
» hyperthermia, especially with MDMA,
» tachycardia,
» hypertension,
» angina pectoris and myocardial infarction,
» stroke,
» hyperactivity,
» delirium,
» tremors, and
» seizures and coma.
2015
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CHAPTER 19
POISONING
Additional complications include:
» rhabdomyolysis,
» hyperkalaemia,
» acute tubular necrosis,
» hyponatraemia,
» dehydration.
GENERAL MEASURES
Supportive management aims to maintain stable cardiorespiratory function.
Manage hyperthermia, hypoglycaemia, dehydration, and electrolyte
abnormalities.
MEDICINE TREATMENT
Haemodialysis may be required for acute renal failure.
For seizures:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
Severe hypertension:
See section 3.6.1: Hypertension, severe.
19.15 HYDROCARBON POISONING
T52.0
DESCRIPTION
Poisoning due to petroleum products, including paraffin, turpentine, petrol,
mineral spirits and halogenated hydrocarbons.
Clinical signs include:
» chemical pneumonitis,
» GIT effects,
» arrhythmias, and
» CNS effects.
GENERAL MEASURES
If contaminated, remove clothing and wash skin.
Do not induce emesis or attempt gastric emptying/lavage.
MEDICINE TREATMENT
Activated charcoal is of no value.
Observe and examine for chemical pneumonitis. Prophylactic antibiotics are
not indicated.
2015
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POISONING
19.16 INGESTION OF CAUSTIC SUBSTANCES
T54.3/T54.2
DESCRIPTION
Alkaline: Toilet bowl cleaners, drain cleaners, oven cleaners.
Acids: Various e.g. domestic descalers.
Caustic substances cause tissue necrosis of the gut resulting in strictures later.
GENERAL MEASURES
No emesis or gastric lavage.
Rinse mouth with copious amounts of cold water.
Patients may require urgent endoscopic evaluation and possible surgical
intervention. (Discuss with a specialist).
19.17 ALCOHOLS
19.17.1 ETHANOL POISONING
T51.0
DESCRIPTION
Acute poisoning usually presents with:
» nausea and vomiting,
» central nervous system depression,
» hypoglycaemia,
» hypothermia,
» hypokalaemia
» hyponatraemia, and
» acidosis.
Consider other causes for the patient’s condition, including hypoglycaemia
and head trauma.
GENERAL MEASURES
Supportive management aimed at maintaining stable cardiorespiratory function.
Protect the airway (ventilation may be needed).
Manage hypothermia, hypoglycaemia, and electrolyte abnormalities.
MEDICINE TREATMENT

Thiamine, IV, 100 mg in 1 L dextrose 5%.
2015
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CHAPTER 19
POISONING
19.17.2 ETHYLENE GLYCOL POISONING
T52.3
DESCRIPTION
Ethylene glycol is a component of motor vehicle radiator coolant/antifreeze
and brake fluid. It is also found in homemade toilet and drain cleaners.
Mild to moderate intoxication: Resembles alcohol intoxication, with nausea
and vomiting, nystagmus, ataxia and somnolence.
Severe intoxication: Associated with more severe CNS depression (coma,
+
–
hypotonia, hyporeflexia), high anion gap metabolic acidosis (i.e. [Na ] – ([Cl ]
–
+ [HCO3 ]) > 12), and renal failure.
Cardiovascular signs include tachycardia and hypertension. Hypocalcaemia
due to calcium oxalate crystals.
One to two weeks after severe intoxication, crystals may cause cranial nerve
abnormalities.
GENERAL MEASURES
Immediate consultation with a poison centre is important.
Early treatment with alcohol prevents formation of toxic metabolites.
Monitor blood gases and administer sodium bicarbonate, IV, to keep the pH
above 7.2 (this decreases end organ damage by toxic metabolites).
Early haemodialysis is the treatment of choice with severe poisoning or
profound acidosis.
MEDICINE TREATMENT
Ethanol

Ethanol 95% BP, oral, diluted to 20% in any suitable liquid.
o Loading dose: 4 mL/kg
o Maintenance dose: non-drinker:
0.4–0.7 mL/kg/hour
chronic drinker: 0.8 mL/kg/hour
xxviii
LoE:III
If ethanol 95% BP is not available, administer any commercially available
alcoholic beverage with an alcohol content of ± 40% e.g. whiskey (80 proof),
diluted 1:2.
Note:
» If patients are not co-operative, administer ethanol via a nasogastric tube.
» Maintain plasma ethanol levels of 1–1.3 g/L (100–130 mg/dL).
» Several days of ethanol therapy may be required. Continue treatment
until clinical condition improves.
Cofactor therapy:

Thiamine, oral, 100 mg daily.

Pyridoxine, oral, 100 mg daily.
LoE:III
2015
19.26
CHAPTER 19
POISONING
Metabolic acidosis
The aim is to increase the pH to 7.2:

Sodium bicarbonate, IV, 50–100 mmol/L administered over 30–45
minutes.
Note: The rapid infusion of large volumes of sodium bicarbonate in an
already oliguric patient may precipitate pulmonary oedema and cardiac
dysrhythmias.
Monitor glucose levels and correct hypoglycaemia, if necessary.
Correct severe or clinical evident hypocalcaemia.
19.17.3 METHANOL POISONING
T51.1
DESCRIPTION
Previously found in methylated spirits but methanol has recently been
replaced with less toxic agents. Also found in antifreeze and windscreen
washes. Methanol does not cause an ethanol-like inebriation.
Presents with:
» Initially, headache, confusion, nausea and vomiting.
» Later, high anion gap (> 12), metabolic acidosis, retinal toxicity (with
visual impairment to total blindness) and renal failure due to formic acid
production.
MEDICINE TREATMENT
If acidotic and there is an increased osmolar gap:
[measured osmolarity minus calculated (2 {sodium+potassium}+ urea+
glucose)], start with immediate ethanol therapy and evaluate for urgent
dialysis, if available.
LoE:III
See section 19.15.2: Ethylene glycol poisoning.
19.18 PESTICIDES AND RODENTICIDES
19.18.1 AMITRAZ POISONING
T60.9
* Notifiable condition.
DESCRIPTION
Amitraz is a pesticide/insecticide which is an α2-adrenergic agonist. It is usually
formulated as a tick dip for dogs, cattle and sheep. Commercial formulations
contain up to 20% of amitraz in organic solvents. Poisoning may occur when
amitraz is ingested or absorbed via the skin or by inhalation.
2015
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POISONING
Patients with acute poisoning present with:
» impaired consciousness
» bradycardia
» drowsiness
» tachypnoea
» vomiting
» hypothermia
» hypotension
» generalized seizures
» constricted pupils or rarely, dilated pupils
Other complications include:
» hyperglycaemia
» glycosuria
» mild increase in transaminases
Patients usually regain consciousness within 24 hours.
Note: Amitraz poisoning can be confused with organophosphate poisoning;
however, organophosphate toxicity presents with reduced serum
pseudocholinesterase.
GENERAL MEASURES
Decontamination of skin and clothes where applicable.
Supportive and symptomatic treatment to maintain patent airway, adequate
respiration and circulation.
Mechanical ventilation may be needed in some cases.
Keep patient warm.
MEDICINE TREATMENT
For severe bradycardia:
 Atropine (See section 3.3.3 Heart block (second or third
degree)).
LoE:III
For seizures:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
19.18.2 ORGANOPHOSPHATE POISONING
T60.0
* Notifiable condition.
DESCRIPTION
Absorption occurs through the skin, when the agent is taken orally, or by
inhalation.
Patients present with muscarinic and nicotinic manifestations of intoxication.
Muscarinic overstimulation: salivation, lacrimation, vomiting, diarrhoea and
increased bronchial secretions, with bronchospasm and miosis (pin point pupils).
Nicotinic overstimulation: muscle fasciculations and paresis or paralysis and
often hypertension. Patients may present with either bradycardia or tachycardia.
Diagnosis is supported by low serum pseudocholinesterase levels.
2015
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CHAPTER 19
POISONING
GENERAL MEASURES
Decontamination of skin and clothes, where applicable.
Maintain adequate ventilation and circulation.
Ventilatory support in ICU may be required due to excess of nicotinic effects.
MEDICINE TREATMENT

Atropine, IV, 2–5 mg, as a single dose, while monitoring patient for
pulmonary muscarinic symptoms and signs.
o Double the dose every five minutes until symptoms are alleviated. A
continuous IV infusion of 0.05 mg/kg/hour may be required for
continuous atropinisation.
o Do not stop atropine therapy abruptly. Wean at a rate of no more
than 1–2 mL/hour. During this phase it is important to monitor the
patient as a worsening in condition commonly occurs a few days
following ingestion.
xxix
LoE:II
19.18.3 PARAQUAT POISONING
T60.3
* Notifiable condition.
DESCRIPTION
Paraquat poisoning causes multi-organ failure and can be fatal. Following
oral ingestion, patients present with oral, oesophageal and gastric erosions
with severe gastroenteritis. Multi-organ failure develops within 1–3 days.
Patients surviving the initial phase usually develop pulmonary fibrosis.
GENERAL MEASURES
Supportive and symptomatic management to maintain patent airway,
adequate respiration and circulation. Mechanical ventilation maybe needed
in some cases.
Note: High inspiratory fraction of inspired oxygen (FiO2) may worsen
pulmonary toxicity. Supplemental oxygen should only be provided if the
patient is confirmed hypoxic.
MEDICINE TRETAMENT

Activated charcoal if patient presents within 1–2 hours after ingestion.
19.19 ANTICOAGULANT POISONING
T45.5
DESCRIPTION
Poisoning due to warfarin ingestion and ingestion of superwarfarins, e.g. rat
poison and other vermin poisons. Warfarin poisoning can occur following an
intentional ingestion of a large amount of warfarin.
2015
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CHAPTER 19
POISONING
It can also occur unintentionally, during chronic ingestions of prescribed
amounts, whereby drug interactions increase the bioavailability of warfarin
(e.g. concomitant enzyme inhibitor), or concomitant anticoagulant drugs are
administered (e.g. NSAIDS). Bleeding is the main clinical presentation e.g.
gastrointestinal or intracranial bleeding; however bleeding may be occult.
Superwarfarins are very potent, therefore even a small amount can lead to
serious complications, and have a very long duration of effect. Measure INR
at baseline and 48 hours post ingestion, as the anticoagulant effect may be
delayed by 1–2 days.
GENERAL MEASURES
Resuscitation.
Stop warfarin in patients on therapy.
MEDICINE TREATMENT
For patients on warfarin therapy
INR 5 to 9 without bleeding:
» Stop warfarin
» Evaluate bleeding risk
- High risk patients: (history of bleeding, stroke, renal insufficiency,
anaemia, hypertension).

Vitamin K1 oral, 1–2.5 mg, for 1–2 days and monitor INR.
- Low risk patients: Monitor INR.
INR > 9 without bleeding:
» Stop warfarin.

Vitamin K1 oral, 2.5–5 mg, for 1–2 days and monitor INR (response
usually in 24 to 48 hrs).
» Resume warfarin therapy, at a lower dose.
Vitamin K1 is available as a parenteral preparation only, but can be given
xxx
orally.
LoE:I
Elevated INR with significant bleeding:
» Stop warfarin.

Vitamin K1, IV,10 mg diluted in 100 mL sodium chloride 0.9% over 20
xxxi
minutes and monitor for anaphylaxis.
LoE:III

Give FFP 15 mL/kg
xxxii
OR
LoE:III
Lyophilised plasma, IV, 15 mL/kg.
xxxiii
LoE:II
Note:
»
In patients with prosthetic heart valves high dose vitamin K is associated
with increased resistance to warfarin and increased risk of
thromboembolism. Treat as above, but monitor INR frequently to
prevent overcorrection.
2015
19.30
CHAPTER 19
»
»
POISONING
In all patients on therapeutic warfarin a major overdose or bleeding
episode should prompt careful review of the need for anticoagulation
If warfarin is indicated it should be re-instituted, once the INR is in the
therapeutic range.
Super warfarins
» Treatment with vitamin K1 needs to be prolonged for several months as
these substances are very long acting.
» Monitor INR according to clinical response.

Vitamin K1 oral, 10–25 mg, daily may be required.
Vitamin K1 is available in the public sector as a parenteral preparation only, but
this can be given orally.
19.20 CARBON MONOXIDE POISONING
T58
DESCRIPTION
Poisoning caused by accidental or intentional exposure to fires in poorly
ventilated areas, combustion engines, faulty stoves and faulty heating systems.
Patients present with:
» dizziness
» impaired level of consciousness
» seizures and other CNS symptoms
» cherry red skin and lips
» nausea and vomiting
» tachycardia
» headache
»
» retinal haemorrhages
» normal arterial PaO2 but low
» high arterial
oxygen saturation
carboxyhaemoglobin - test not
commonly available
GENERAL MEASURES
Remove patient from toxic environment.
Ventilation may be needed in deeply comatose patients.
In a Cochrane review, hyperbaric oxygen therapy has not been shown
to be of benefit.
MEDICINE TREATMENT
Give 100% oxygen via facemask.
For seizures:
 Diazepam IV, 10 mg as a single dose.
o If seizures persist refer to section 14.3.1 Status epilepticus for
management to stop seizures.
2015
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CHAPTER 19
POISONING
19.21 HEAVY METAL POISONING
T56.1/T57.0/T56.8/T56.4/T56.0/T56.3
DESCRIPTION
This includes mercury, arsenic, gold, copper, lead poisoning etc. Acute
toxicity of organ-systems may be summarised as follows:
Discuss all potential patients with poison centre for further investigation,
treatment and possible referral.
Mercury
Arsenic
Gold
Thallium
Copper
Lead
Cadmium
Respiratory
x
x
GIT
x
x
x
x
x
x
x
Haematological
x
x
x
x
x
x
CVS
Kidneys
x
x
x
x
X
x
x
x
x
x
x
x
Hepatotoxicity
CNS
x
x
x
x
x
x
x
19.22 POISONING WITH SUBSTANCES THAT CAUSE
METHAEMOGLOBINAEMIA
D74.8/D74.9
DESCRIPTION
Nitrites are used to cure meat in the formal and informal butchery sector.
Patients present with:
» normal oxygen levels and deep central cyanosis, due to
methaemoglobinaemia,
» CNS depression, and
» arrhythmias.
Note: Mild methaemoglobinaemia causes patients to appear cyanosed with
falsely low pulse oximetry readings. An arterial blood gas analysis should be
done.
MEDICINE TREATMENT
Oxygen via facemask.
In symptomatic cases or patients with high methaemoglobin values > 30%:
 Methylene blue (methylthioninium chloride) 1% dilute solution, slow IV
infusion, 1–2 mg/kg administered over 5 minutes.
o Repeat in 1 hour and, if necessary, 4 hourly up to total of 7 mg/kg.
o Side effects include praecordial pain, restlessness and dyspnoea.
2015
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CHAPTER 19
o
POISONING
After administration of methylene blue, oxygen saturation may drop
initially.
In life-threatening cases, not responding to methylene blue or if methylene
blue is not available, exchange transfusion may be considered. There are
isolated case reports of use with N-acetylcysteine or high doses of ascorbic
acid (vitamin C). Consult with poison information centre for management.
xxxiv
LoE:III
References:
i
Amoxicillin/clavulanic acid, oral: Blaylock RS. Antibiotic use and infection in snakebite victims. S Afr Med J. 1999
Aug;89(8):874-6. http://www.ncbi.nlm.nih.gov/pubmed/10488365
ii NSAID caution: World Health Organisation: Guidelines for the prevention and clinical management of snakebite in
Africa. http://www.afro.who.int/en/clusters-a-programmes/hss/essential-medicines/highlights/2731-guidelines-for-theprevention-and-clinical-management-of-snakebite-in-africa.html
iii Polyvalent antivenom: Wood D, Webb C, DeMeyer J. Severe snakebites in northern KwaZulu-Natal: treatment
modalities and outcomes. S Afr Med J. 2009 Nov;99(11):814-8. http://www.ncbi.nlm.nih.gov/pubmed/20218483
Polyvalent antivenom: Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Snake bite in southern Africa:
diagnosis and management. CME Oct 2012; 30(10):362-82.
http://www.cmej.org.za/index.php/cmej/article/view/2546/2581
iv
Adrenaline (epinephrine), SC: de Silva HA, Pathmeswaran A, Ranasinha CD, Jayamanne S, Samarakoon SB,
Hittharage A, Kalupahana R, Ratnatilaka GA, Uluwatthage W, Aronson JK, Armitage JM, Lalloo DG, de Silva HJ. Lowdose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following
snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011 May;8(5):e1000435.
http://www.ncbi.nlm.nih.gov/pubmed/21572992
Adrenaline (epinephrine), SC: Nuchpraryoon I, Garner P. Interventions for preventing reactions to snake antivenom.
Cochrane Database Syst Rev. 2000;(2):CD002153. Review. http://www.ncbi.nlm.nih.gov/pubmed/21572992
v
Polyvalent antivenom: Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Snake bite in southern Africa:
diagnosis and management. CME Oct 2012; 30(10):362-82.
http://www.cmej.org.za/index.php/cmej/article/view/2546/2581
Polyvalent antivenom: SAMF, 2014.
vi
Boomslang antivenom: Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Snake bite in southern Africa:
diagnosis and management. CME Oct 2012; 30(10):362-82.
http://www.cmej.org.za/index.php/cmej/article/view/2546/2581
vii
Paracetamol, oral: Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Scorpion sting in southern Africa:
diagnosis and management. CME Oct 2012; 30(10):356-61.
http://www.cmej.org.za/index.php/cmej/article/view/2545/2580
viii
Lidocaine. 1-2%, infiltration: Aksel G, Güler S, Doğan N, Corbacioğlu S. A randomized trial comparing
intravenous paracetamol, topical lidocaine, and ice application for treatment of pain associated with scorpion
stings. Hum Exp Toxicol. 2014 Oct 10. pii: 0960327114551394. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/25304965
Lidocaine. 1-2%, infiltration: Paediatric Hospital level STGs and EML, 2013. 2013. http://www.health.gov.za/
Lidocaine. 1-2%, infiltration: Chippaux JP. Emerging options for the management of scorpion stings. Drug Des
Devel Ther. 2012;6:165-73. http://www.ncbi.nlm.nih.gov/pubmed/22826633
Lidocaine. 1-2%, infiltration: Contract circular HP06-2014SVP. http://www.health.gov.za/
ix
Opiates (caution): Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Scorpion sting in southern Africa:
diagnosis and management. CME Oct 2012; 30(10):356-61.
http://www.cmej.org.za/index.php/cmej/article/view/2545/2580
x
Spider antivenom: Muller GJ, Wium CA, Marks CJ, du Plessis CE, Veale DJH. Spider bite in southern Africa:
diagnosis and management. CME October 2012;30(10): 382-91.
http://www.cmej.org.za/index.php/cmej/article/view/2547/2582
xi
Gastric lavage: Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J, Mégarbane B, Thanacoody
R, Caravati EM; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical
Toxicologists. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila). 2013
Mar;51(3):140-6. http://www.ncbi.nlm.nih.gov/pubmed/23418938
xii
Activated charcoal (multi-dose): Position statement and practice guidelines on the use of multi-dose activated
charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of
Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1999;37(6):731-51.
http://www.ncbi.nlm.nih.gov/pubmed/10584586
xiii
Paracetamol nomogram: Daly FF, Fountain JS, Murray L, Graudins A, Buckley NA; Panel of Australian and New
Zealand clinical toxicologists. Guidelines for the management of paracetamol poisoning in Australia and New
Zealand - -explanation and elaboration. A consensus statement from clinical toxicologists consulting to the
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POISONING
Australasian poisons information centres. Med J Aust. 2008 Mar 3;188(5):296-301.
http://www.ncbi.nlm.nih.gov/pubmed/18312195
xiv
Activated charcoal: Bradberry SM, Vale JA. Multiple-dose activated charcoal: a review of relevant clinical
studies. J Toxicol Clin Toxicol. 1995;33(5):407-16. Review. http://www.ncbi.nlm.nih.gov/pubmed/7650765
Whole bowel irrigation: Mayer AL, Sitar DS, Tenenbein M. Multiple-dose charcoal and whole-bowel irrigation do
not increase clearance of absorbed salicylate. Arch Intern Med. 1992 Feb;152(2):393-6.
http://www.ncbi.nlm.nih.gov/pubmed/1739372
xv
Naloxone: SAMF, 2014
Naloxone: FDA approved package insert – Hospira Inc.: Naloxone Hydrochloride, 2015.
http://medlibrary.org/lib/rx/meds/naloxone-hydrochloride-8/
xvi
Flumazenil : Penninga EI, Graudal N, Ladekarl MB, Jürgens G. Adverse Events Associated with Flumazenil
Treatment for the Management of Suspected Benzodiazepine Intoxication - A Systematic Review with MetaAnalyses of Randomised Trials. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):37-44.
http://www.ncbi.nlm.nih.gov/pubmed/26096314
xvii
Desferrioxamine, IV: Tenenbein M. Benefits of parenteral deferoxamine for acute iron poisoning. J Toxicol Clin
Toxicol. 1996;34(5):485-9. http://www.ncbi.nlm.nih.gov/pubmed/8800185
Desferrioxamine, IV: Tenenbein M, Kowalski S, Sienko A, Bowden DH, Adamson IY. Pulmonary toxic effects of
continuous desferrioxamine administration in acute iron poisoning. Lancet. 1992 Mar 21;339(8795):699-701.
http://www.ncbi.nlm.nih.gov/pubmed/1347583
xviii
Desferrioxamine, IV (pregnancy): Liebelt EL, Kronfol R, Burns MM, Traub SJ, Wiley JF. Acute Iron Poisoning.
UpToDate - Narrative review, August 2015. http://www.uptodate.com/contents/acute-iron-poisoning
xix
Activated charcoal: SAMF, 2014.
xx
Flumazenil: Penninga EI, Graudal N, Ladekarl MB, Jürgens G. Adverse Events Associated with Flumazenil
Treatment for the Management of Suspected Benzodiazepine Intoxication - A Systematic Review with MetaAnalyses of Randomised Trials. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):3744.http://www.ncbi.nlm.nih.gov/pubmed/26096314
xxi
Polyethylene glycol: Bretaudeau Deguigne M, Hamel JF, Boels D, Harry P. Lithium poisoning: the value of early
digestive tract decontamination. Clin Toxicol (Phila). 2013 May;51(4):243-8.
http://www.ncbi.nlm.nih.gov/pubmed/23566313
xxii
Pyridoxine: Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005
Apr;12(2):78-85. http://www.ncbi.nlm.nih.gov/pubmed/15756083
xxiii
Sodium chloride, 0.9%, IV: Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg
Med. 1995 Jul;13(4):444-50. http://www.ncbi.nlm.nih.gov/pubmed/7605536
xxiv
Atropine, IV: Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg Med. 1995
Jul;13(4):444-50. http://www.ncbi.nlm.nih.gov/pubmed/7605536
xxv
Calcium gluconate 10%, IV: Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg
Med. 1995 Jul;13(4):444-50. http://www.ncbi.nlm.nih.gov/pubmed/7605536
xxvi
Dextrose 50%, IV: Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg Med. 1995
Jul;13(4):444-50. http://www.ncbi.nlm.nih.gov/pubmed/7605536
Dextrose 50%, IV: Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulin is a superior antidote for
cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther. 1993 Nov;267(2):74450. http://www.ncbi.nlm.nih.gov/pubmed/8246150
Dextrose 50%, IV: Greene SL, Gawarammana I, Wood DM, Jones AL, Dargan PI. Relative safety of
hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective
observational study. Intensive Care Med. 2007 Nov;33(11):2019-24. Epub 2007 Jul 11.
http://www.ncbi.nlm.nih.gov/pubmed/17622512
Dextrose 50%, IV: Patel NP, Pugh ME, Goldberg S, Eiger G. Hyperinsulinemic euglycemia therapy for verapamil
poisoning: a review. Am J Crit Care. 2007 Sep;16(5):498-503. http://www.ncbi.nlm.nih.gov/pubmed/17724247
Short acting insulin: Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg Med. 1995
Jul;13(4):444-50. http://www.ncbi.nlm.nih.gov/pubmed/7605536
Short acting insulin: Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulin is a superior antidote for
cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther. 1993 Nov;267(2):74450. http://www.ncbi.nlm.nih.gov/pubmed/8246150
Short acting insulin: Greene SL, Gawarammana I, Wood DM, Jones AL, Dargan PI. Relative safety of
hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective
observational study. Intensive Care Med. 2007 Nov;33(11):2019-24. http://www.ncbi.nlm.nih.gov/pubmed/17622512
Short acting insulin: Patel NP, Pugh ME, Goldberg S, Eiger G. Hyperinsulinemic euglycemia therapy for verapamil
poisoning: a review. Am J Crit Care. 2007 Sep;16(5):498-503. http://www.ncbi.nlm.nih.gov/pubmed/17724247
xxvii
Haloperidol, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
Lorazepam, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
Midazolam, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
Clonazepam, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
2015
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Diazepam, IV: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
Promethazine, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
Chlorpromazine, IM: Adult Hospital level STG, 2015. Section 15.1 Aggressive disruptive behaviour.
http://www.health.gov.za/
xxviii
Ethanol: Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology Practice
Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol.
1999;37(5):537-60. http://www.ncbi.nlm.nih.gov/pubmed/10497633
xxix
Atropine, IV: Abedin MJ, Sayeed AA, Basher A, Maude RJ, Hoque G, Faiz MA. Open-label randomized clinical
trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in
Bangladesh. J Med Toxicol. 2012 Jun;8(2):108-17. http://www.ncbi.nlm.nih.gov/pubmed/22351300
xxx
Vitamin K1, oral: Dezee KJ, Shimeall WT, Douglas KM, Shumway NM, O'malley PG. Treatment of
excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med. 2006 Feb
27;166(4):391-7. http://www.ncbi.nlm.nih.gov/pubmed/16505257
Vitamin K1, oral: Crowther MA, Douketis JD, Schnurr T, Steidl L, Mera V, Ultori C, Venco A, Ageno W. Oral vitamin
K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarinassociated coagulopathy. A randomized, controlled trial. Ann Intern Med. 2002 Aug 20;137(4):251-4.
http://www.ncbi.nlm.nih.gov/pubmed/12186515
xxxi
Vitamin K1, IV: Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL,
Crowther M, Guyatt GH; American College of Chest Physicians. Evidence-based management of anticoagulant
therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-84S.
http://www.ncbi.nlm.nih.gov/pubmed/22315259
xxxii
Fresh frozen plasma: Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G; American College of
Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S.
http://www.ncbi.nlm.nih.gov/pubmed/18574265
xxxiii
Lyophilised plasma: Lerner RG, Nelson J, Sorcia E, Grima K, Kancherla RR, Zarou-Naimo CM, Pehta JC.
Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang.
2000;79(3):161-7. http://www.ncbi.nlm.nih.gov/pubmed/11111235
Lyophilised plasma: Huisman EL, de Silva SU, de Peuter MA. Economic evaluation of pooled solvent/detergent
treated plasma versus single donor fresh-frozen plasma in patients receiving plasma transfusions in the United States.
Transfus Apher Sci. 2014 Aug;51(1):17-24. http://www.ncbi.nlm.nih.gov/pubmed/25151097
xxxiv
Ascorbic acid: Park SY, Lee KW, Kang TS. High-dose vitamin C management in dapsone-induced
methemoglobinemia. Am J Emerg Med. 2014 Jun;32(6):684.e1-3. http://www.ncbi.nlm.nih.gov/pubmed/24439259
N-acetylcysteine: Wright RO, Magnani B, Shannon MW, Woolf AD. N-Acetylcysteine reduces methemoglobin in
vitro. Ann Emerg Med 1996;28: 499-503. http://www.ncbi.nlm.nih.gov/pubmed/8909270
2015
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20.1 EMERGENCIES
20.1.1 ANGIOEDEMA
T78.3
DESCRIPTION
Angioedema is well demarcated, localised oedema involving deeper layers
of skin and subcutaneous tissue.
ACE-inhibitors are the most common cause, mediated by reduced
bradykinin. Hereditary or acquired deficiencies of C1 esterase inhibitor,
resulting in reduced bradykinin, are uncommon causes of angioedema.
Treatment of these causes of angioedema is to increase bradykinin, e.g. by
giving fresh frozen plasma, which contains C1 esterase inhibitor and ACE.
The other mechanism of angioedema is type 1 hypersensitivity reactions to
medicines and other exogenous substances (e.g. food). Other manifestations
of allergy (e.g. urticaria, bronchospasm, anaphylaxis) may be present.
Symptoms
Swelling usually occurs around eyes and lips but may occur elsewhere.
Life-threatening airway obstruction can occur with angioedema of the upper
airways.
GENERAL MEASURES
Stop all suspected agents, e.g. ACE-inhibitor.
In case of angioedema with airway obstruction, early airway management is
essential. If oedema is extensive or progressive, establish a definitive airway.
The most skilled person available must handle airway interventions.
Avoid re-exposure to the offending agent and provide an alert bracelet.
MEDICINE TREATMENT
In severe cases of hypersensitivity where airway obstruction may be imminent:
Note: A surgical airway may be required before patient responds to medical
treatment.
 Adrenaline (epinephrine) 1:1000, 0.5 mL, IM, immediately into
anterolateral thigh.
LoE:IIIi
o Repeat dose every 5 minutes, as required.
In cases where angioedema is part of anaphylaxis, treat as
anaphylaxis. See section 20.1.2: Anaphylaxis/Anaphylactic shock.

Hydrocortisone, IV, 100 mg as a single dose.
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EMERGENCIES AND INJURIES
If urticaria and/or itch present:

Antihistamine, e.g.:

Cetirizine, oral, 10 mg daily.
LoE:III
Observe all cases until resolution.
Severe ACE-inhibitor induced angioedema with threatened airway:
Note: A surgical airway may be required before patient responds to medical
treatment.

FFP, IV, 2 units.
LoE:IIii
OR
Lyophilised plasma, IV, at an equivalent dose.
LoE:III
20.1.2 ANAPHYLAXIS/ANAPHYLACTIC SHOCK
T78.2
DESCRIPTION
An acute, potentially life-threatening hypersensitivity reaction.
The reaction usually starts within seconds to minutes after administration of,
or exposure to a substance to which the individual has been sensitised.
Clinical manifestations range from mild urticaria and angioedema to upper
airway obstruction, bronchospasm, hypotension, shock and death.
The reaction can be short-lived, protracted or biphasic, i.e. acute with
recurrence several hours later.
Immediate reactions are usually the most severe and/or life threatening.
GENERAL MEASURES
Administer adrenaline (epinephrine) immediately (see below)
Cardiopulmonary resuscitation, if required.
Maintain an open airway. Intubate, if necessary.
Monitor all vital parameters (including pulse and blood pressure) closely.
Reassure and comfort the patient.
Patient counselling to prevent recurrence.
An alert bracelet should be worn at all times.
MEDICINE TREATMENT

Adrenaline (epinephrine) 1:1000, 0.5 mL,
anterolateral thigh.
o Repeat dose every 5 minutes, as required.
IM,
immediately
Intravenous fluids
Establish an intravenous line:

Sodium chloride 0.9%, IV.
AND

Hydrocortisone, IV, 200 mg, immediately as a single dose.
2015
into
LoE:IIiii
20.2
CHAPTER 20
EMERGENCIES AND INJURIES
If bronchospasm:

Oxygen.
AND

Salbutamol 5 mg (1 mL 0.5% respiratory solution with 4 mL sodium
chloride 0.9%).
LoE:IIIiv
o Nebulise continuously (refill the nebuliser reservoir
every 20 minutes) at a flow rate of 6–8 L/minute.
If urticaria and/or itch present:

Antihistamine, e.g.:

Cetirizine, oral, 10 mg as a single dose.
LoE:III
20.1.3 HYPOVOLAEMIC SHOCK
R57.1
DESCRIPTION
This happens when there is loss of intravascular fluid, e.g. severe diarrhoea
and dehydration, haemorrhage or fluid shifts.
GENERAL MEASURES
Control obvious bleeding with direct pressure. Do not use tourniquets.
Insert one or two large bore IV catheters; peripheral lines are adequate.
MEDICINE TREATMENT
Initial volume resuscitation
 Sodium chloride 0.9%, IV, 1–2 L.
Monitor blood pressure, pulse and clinical response.
LoE:Iv
Trauma-related haemorrhage
May be given within 3 hours of injury:

Tranexamic acid, IV, 1 g, infused over 10 minutes.
LoE:Ivi
o Followed with IV infusion, 1 g, over 8 hours.
st
Benefit is greatest, if initiated, in the 1 hour. Initiation beyond 3 hours of
tranexamic acid may be harmful.
Blood transfusion, if indicated.
If patient responds initially and subsequently deteriorates, there may be an
ongoing occult haemorrhage. If no response occurs, consider:
» Occult exsanguinating haemorrhage: intra-abdominal, retroperitoneal
and intrapleural.
» Non-hypovolaemic shock: tension pneumothorax, myocardial contusion,
cardiac tamponade or myocardial infarct.
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20.1.4 DISTRIBUTIVE SHOCK
R65.1/R57.9
This happens when the blood vessels are abnormally dilated and presents
with a low blood pressure, tachycardia and warm peripheries. There are 3
causes of this type of shock:
» neurogenic shock,
»
septic shock, and
» anaphylactic shock (see section: 20.1.2 Anaphylaxis/anaphylactic shock).
20.1.4.1 NEUROGENIC SHOCK
R57.8
DESCRIPTION
Occurs in spinal cord trauma when there is an interruption of the sympathetic
chain causing vasodilatation.
GENERAL MEASURES
Check circulation, airway and breathing.
Spinal cord immobilisation.
Exclude other injuries that could cause low blood pressure.
MEDICINE TREATMENT
If hypoxic:

Oxygen.

Adrenaline (epinephrine), IV infusion, start at 0.05 mcg/kg/minute titrated
according to the response.
o Dilute 10 mg i.e. 10 ampoules of adrenaline 1:1 000 in 1 L sodium
chloride 0.9%.
o Infuse according to weight and clinical response.
o Infusion rate: mL/hour:
Weight in kg
mcg/kg/minute
50
60
70
80
90
100
110
0.05
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
2015
15
30
60
90
120
150
180
210
240
270
300
18
36
72
108
144
180
216
252
288
324
360
21
42
84
126
168
210
252
294
336
378
420
24
48
96
144
192
240
288
336
384
432
480
27
54
108
162
216
270
324
378
432
486
540
30
60
120
180
240
300
360
420
480
540
600
33
66
132
198
264
330
396
462
528
594
660
20.4
CHAPTER 20
EMERGENCIES AND INJURIES
20.1.4.2 SEPTIC SHOCK
R57.2
DESCRIPTION
Shock caused by a confirmed or suspected infection, with vasodilatation,
increased capillary permeability, and decreased contractility of the heart.
GENERAL MEASURES
Check airway, breathing and circulation.
MEDICINE TREATMENT
If hypoxic:

Oxygen.
Take blood culture, then administer appropriate parenteral broad spectrum
antibiotics urgently, e.g.:
 Ceftriaxone, IV, 2 g daily.
LoE:IIvii
Perform a fluid challenge for hypotension:

Sodium chloride 0.9%, IV, 500 mL over 30 minutes.
o Assess blood pressure and pulse rate response. Response is
defined by a good urine output (> 0.5 ml/kg/hour) and adequate
cerebral perfusion rather than an absolute blood pressure value.
LoE:III
If there is a positive response, continue with intravenous fluid.
Avoid over-hydrating as this could exacerbate hypoxia associated with adult
respiratory distress syndrome.
If no haemodynamic response to fluid challenge:
 Adrenaline (epinephrine), IV infusion, 0.05 mcg/kg/minute titrated
according to the response.
o Dilute 10 mg i.e. 10 ampoules of adrenaline 1:1000 in 1 L sodium
chloride 0.9%.
o Infuse according to weight and clinical response.
o See section 20.1.4.1: Neurogenic shock, for the infusion rate.
20.1.5 CARDIOGENIC SHOCK
R57.0
DESCRIPTION
Patients are hypotensive, cold and clammy and their pulse rate may be
variable. Causes include an acute myocardial infarction (MI), myocardial
contusion, myocarditis, dysrhythmias, valvular heart disease, etc.
GENERAL MEASURES
Check circulation, airway and breathing.
ECG.
2015
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EMERGENCIES AND INJURIES
MEDICINE TREATMENT
If hypoxic:

Oxygen.
Treat the underlying cause, e.g.: MI, dysrhythmia, etc.
A right ventricular myocardial infarction may respond to a fluid challenge.

Dobutamine, infusion, 5–10 mcg/kg/minute.
o Dilute 1 vial (250 mg/20 mL) up to 50 mL with sodium chloride 0.9%
or dextrose 5% (5 mg/mL or 5 000 mcg/mL).
LoE:IIIviii
o Rate of infusion in mL/hour:
Weight (kg)
Dose mcg/kg/min
30
40
50
60
70
80
90
100
110
120
2
0.9
1.2
1.5
1.8
2.1
2.4
2.7
3
3.3
3.6
5
1.8
2.4
3
3.6
4.2
4.8
5.4
6
6.6
7.2
7.5
2.7
3.6
4.5
5.4
6.3
7.2
8.1
9
9.9
10.8
10
3.6
4.8
6
7.2
8.4
9.6
10.8
12
13.2
14.4
20.1.6 OBSTRUCTIVE SHOCK
R57.9
DESCRIPTION
Occurs when there is an obstruction to the filling of the right ventricle or an
obstruction in blood flow. Clinical signs include hypotension, tachycardia and
cold peripheries.
Causes include:
» cardiac tamponade,
» tension pneumothorax,
» acute pulmonary embolism, and
» severe bronchospasm.
TREATMENT
Treat the cause.
20.1.7 PULMONARY OEDEMA, ACUTE
J81
DESCRIPTION
A life-threatening condition with abnormal accumulation of fluid in the lungs.
Acute heart failure is a common cause.
GENERAL MEASURES
Maintain open airway.
Position in Fowler’s position, unless hypotensive or comatose.
Correct electrolyte disturbances.
2015
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EMERGENCIES AND INJURIES
Determine and correct any dysrhythmias.
MEDICINE TREATMENT

Administer oxygen.

Furosemide, slow IV, 20–80 mg, initial dose.
o May be repeated 15 minutes later if symptoms persist.
Isosorbide dinitrate, SL, 5 mg repeat after 1–2 hours, if necessary.

OR
 Glyceryl trinitrate, IV, 5–200 mcg/minute, titrated to response.
o Start with 5 mcg/minute and increase by 5 mcg/minute every 5
minutes until response or until the rate is 20 mcg/minute.
o If no response after 20 mcg/minute increase by 20 mcg/minute until
response.
LoE:IIIix
o Flush the PVC tube before administering to patient.
o Monitor blood pressure carefully.
Volume of diluent
Glyceryl trinitrate
Concentration of
5 mg/mL
dilution
5 mL (25 mg)
100 mcg/mL
250 mL
10 mL (50 mg)
200 mcg/mL
20 mL (100 mg)
400 mcg/mL
10 mL (50 mg)
100 mcg/mL
500 mL
20 mL (100 mg)
200 mcg/mL
40 mL (200 mg)
400 mcg/mL
Solution
Concentration
(mcg/mL)
Dose
(mcg/min)
5
10
15
20
30
40
60
80
100
120
160
200
100
200
400
mcg/mL
mcg/mL
mcg/mL
solution
solution
solution
Flow rate (microdrops/min = mL/hr)
3
6
9
12
18
24
36
48
60
72
96
–
–
3
–
6
9
12
18
24
30
36
48
60
–
–
–
3
–
6
9
12
15
18
24
30
If distressed, consider adding morphine:
 Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
2015
20.7
CHAPTER 20
EMERGENCIES AND INJURIES
If hypotensive consider inotropic support, e.g.:

Dobutamine, IV infusion, 5–20 mcg/kg/minute.
o
Dilute 1 vial (250 mg/20 mL) up to 50 mL with sodium chloride 0.9%
or dextrose 5%. (Solution = 5 mg/mL or 5 000 mcg/mL.)
o
Administer under constant ECG monitoring.
o
Rate of infusion in mL/hour: see weight-dose table in section 20.1.5:
Cardiogenic shock.
20.2 INJURIES
T14
For trauma-related haemorrhage, presenting within 3 hours of injury, see
section 20.1.3 Hypovolaemic shock.
20.2.1 BURNS
T30.0
DESCRIPTION
Skin and tissue damage caused by:
» exposure to extremes of temperature,
» contact with an electrical current,
» exposure to a chemical agent, and
» radiation.
ASSESSMENT OF BURNS
Depth of burn
SURFACE
wound
/COLOUR
Superficial or
Dry, minor
epidermal
blisters,
erythema
Partial thickness
Blisters, moist
superficial or
superficial dermal
Partial thickness
Moist white or
deep or deep
yellow slough,
dermal
red mottled
Full thickness
(complete loss of
skin)
2015
Dry, charred
whitish, brown
or black
PAIN SENSATION/HEALING
»
»
Painful
Heals within 7 days
»
»
Painful
Heals within 10–14 days
» Less painful
» Heals within a month or more
Generally needs surgical
debridement and skin graft
» Painless, firm to touch
» Healing by contraction of the
margins (generally needs surgical
debridement and skin graft)
20.8
CHAPTER 20
EMERGENCIES AND INJURIES
The figures below are used to calculate body surface area %.
These diagrams indicate percentages for the whole leg/arm/head (and
neck in adults) not just the front or back.
Children ≥8 years and adults
Source: Karpelowsky JS, Wallis L, Madaree A, Rode H; South African Burn Society. South African
Burn Society burn stabilisation protocol. S Afr Med J. 2007 Aug;97(8):574-7.
http://www.ncbi.nlm.nih.gov/pubmed/17966146
GENERAL MEASURES
»
»
»
»
»
»
»
»
Assess airway, breathing and circulation.
Intubate early if burns are inhalational, or in the presence of pharyngeal
burns with soft tissue swelling, as these patients frequently tend to
develop respiratory failure.
Support vital organ function.
Obtain early IV access to administer intravenous fluids
Look for aggravating comorbidities, e.g. seizures, hyperkalaemia, renal
failure.
Clean superficial burns can be managed by occlusive dressings.
Deeper wounds may have to be excised and grafted.
Rehabilitation involving physiotherapy and occupational therapy.
Burn injuries put patients into a hypermetabolic state which requires early
and adequate nutritional support.
MEDICINE TREATMENT
Fluid replacement
Burns ≤ 10% Total Body Surface Area (TBSA):
 Oral fluids.
Burns >10% of TBSA:
 IV fluid for resuscitation.
2015
20.9
CHAPTER 20
EMERGENCIES AND INJURIES
Calculation of fluid replacement
Replacement fluids for burns
» First 24 hours:

Sodium chloride 0.9%, IV.
LoE:Ix
o Calculate total fluid requirement in 24 hours:
Total % burn x weight (kg) x 4 mL.
st
o Give half this volume in the 1 8 hours.
o Administer remaining fluid volume in next 16 hours.
Note: If urine output is not adequate, increase fluids for the next hour by
50%. Continue at a higher rate until urine output is adequate, then resume
normal calculated rate. Aim for urine output 0.5 mL/kg/hr.
LoE:IIIxi
Analgesia
Ensure adequate analgesia particularly at change of dressing, i.e.:
 Morphine, IV, to a total maximum dose of 10 mg (See Appendix II, for
individual dosing and monitoring for response and toxicity).
AND

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
Tetanus prophylaxis
 Tetanus toxoid vaccine, IM, 0.5 mL immediately.
Burn dressing
 Silver sulfadiazine 1% cream, topical.
LoE:III
For ocular burns
 Sodium chloride 0.9% eye washes or irrigations as soon as possible.
Stress ulcer prophylaxis
Feeding patients provides protection against gastric ulcer developing and
prophylaxis is not necessary in patients who are tolerating feeds.
Note: Pharmacokinetic parameters are altered in patients with severe burns,
notably an increased volume of distribution. An appropriate loading dose
should be given of certain medicines, e.g. aminoglycosides. Therapeutic drug
monitoring (TDM) may inform dosing and should be requested, if available.
Discuss the following cases with a burns specialist:
»
»
»
»
»
»
»
Burns > 15% body surface area (BSA) or > 10% BSA if over 50 years.
Burns of face, hands, feet, genitalia, perineum or involving joints.
Electrical burns, including lightning burns.
Chemical burns.
Inhalation injury or burns.
Burns associated with major trauma.
Circumferential burns.
2015
20.10
CHAPTER 20
EMERGENCIES AND INJURIES
20.3 CARDIAC ARREST – CARDIOPULMONARY
RESUSCITATION
Abbreviations: CPR = Cardiopulmonary Resuscitation; PEA = Pulseless Electrical Activity; VF =
Ventricular Fibrillation; VT = Ventricular Tachycardia.
Adapted with permission from the Resuscitation Council of Southern Africa.
www.resuscitationcouncil.co.za
2015
20.11
CHAPTER 20
EMERGENCIES AND INJURIES
20.3.1 CARDIAC ARREST ADULTS
I46.9
DESCRIPTION
Described as the loss of a heart beat and a palpable pulse, irrespective of
the electrical activity captured on ECG tracing. Irreversible brain damage can
occur within 2–4 minutes.
Clinical features include:
» sudden loss of consciousness absent carotid and all other pulses
» loss of spontaneous respiration
EMERGENCY TREATMENT
»
»
»
»
»
»
»
Diagnose rapidly.
Make a note of the time of starting resuscitation.
Place the patient on a firm flat surface and commence resuscitation
immediately.
Call for skilled help and an automated external defibrillator (AED) or
defibrillator.
Initiate CAB (Circulation Airways Breathing) sequence of CPR
(cardiopulmonary resuscitation).
A single powerful precordial thump is recommended for witnessed
cardiac arrest where a defibrillator is not immediately available.
Document medication and progress after the resuscitation.
Cardiopulmonary resuscitation
Circulation
» Check for carotid pulse.
» If there is no pulse or you are not sure, start with chest compressions at
a rate of 100-120 compressions per minute.
Airway and breathing
» To open the airway, lift the chin forward with the fingers of the one hand
and tilt the head backwards with other hand on the forehead. Do not do
this where a neck injury is suspected.
» Insert correctly-sized oropharyngeal airway, if available.
Where neck injury is suspected:
» To open the airway, place your fingers behind the jaw on each side.
» Lift the jaw upwards while opening the mouth with your thumbs (jaw thrust).
» To open the airway, place your fingers behind the jaw on each side.
» If there is no normal breathing, give 2 respirations with bag-valve-mask
resuscitator and face mask.
» The administered breaths must cause visible chest rising in patient. If
not, reposition and try again.
» Repeat the cycle of 30 compressions followed by 2 respirations for 5
cycles and then re-assess for a pulse.
2015
20.12
CHAPTER 20

EMERGENCIES AND INJURIES
Oxygenate with 100% oxygen.
Initiate IV fluids, if able.

Sodium chloride 0.9%, IV.
In pulseless tachydysrhythmias:
» Defibrillate, as indicated.
» Call a doctor, if available, without stopping CPR.
» Continue until spontaneous breathing and/or heart beat returns.
LoE:Ixii
Immediate emergency medicine treatment
Adrenaline (epinephrine) is the mainstay of treatment and should be given
Immediately, IV or endotracheal, when there is no response to initial
resuscitation or defibrillation.

Adrenaline (epinephrine), 1:1 000, 1 mL, IV immediately, as a single
dose.
LoE:Ixiii
o Flush with 5–10 mL IV of sterile water or sodium
chloride, 0.9%.
o Repeat every 3–5 minutes during resuscitation.
If no IV line is available:

Adrenaline (epinephrine), endotracheal, 1:1 000, 2 mL through
endotracheal tube.
o Flush with 5–10 mL of sterile water or sodium chloride 0.9%.
o Repeat every 3–5 minutes during resuscitation.
Assess continuously until the patient shows signs of recovery.
Consider stopping resuscitation attempts and pronouncing death if:
» further resuscitation is clearly clinically inappropriate, e.g. incurable
underlying disease, or
» no success after all the above procedures have been carried out for 30
minutes or longer.
Consider carrying on for longer especially when:
» hypothermia and drowning
» poisoning or drug overdose or carbon monoxide poisoning
2015
20.13
CHAPTER 20
EMERGENCIES AND INJURIES
References:
i
Adrenaline (epinephrine), IM: Pawankar RP, Canonica GW, Holgate ST, Lockey RF. WAO White Book on Allergy.
Wisconsin: World Allergy Organization; 2011. Available at: http://www.worldallergy.org/UserFiles/file/WAO-White-Bookon-Allergy_web.pdf
ii
Fresh frozen plasma: Prematta M, Gibbs JG, Pratt EL, Stoughton TR, Craig TJ. Fresh frozen plasma
for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol. 2007
Apr;98(4):383-8. http://www.ncbi.nlm.nih.gov/pubmed/17458436
Fresh frozen plasma: Hassen GW, Kalantari H, Parraga M, Chirurgi R, Meletiche C, Chan C, Ciarlo J,
Gazi F, Lobaito C, Tadayon S, Yemane S, Velez C. Fresh frozen plasma for progressive and refractory angiotensinconverting
enzyme
inhibitor-induced
angioedema.
J
Emerg
Med.
2013
Apr;44(4):764-72.
http://www.ncbi.nlm.nih.gov/pubmed/23114109
Fresh frozen plasma: Culley CM, DiBridge JN, Wilson GL Jr. Off-Label Use of Agents for Management of Serious or
Life-threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema. Ann Pharmacother. 2016
Jan;50(1):47-59. http://www.ncbi.nlm.nih.gov/pubmed/26416949
iii
Sodium chloride, 0.9%: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill
patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. http://www.ncbi.nlm.nih.gov/pubmed/23450531
Sodium chloride, 0.9%: Bunn F, Trivedi D. Colloid solutions for fluid resuscitation. Cochrane
Database Syst Rev. 2012 Jul 11;7:CD001319. http://www.ncbi.nlm.nih.gov/pubmed/22786474
Sodium chloride, 0.9%: Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid
therapies: effects on kidney function. Cochrane Database Syst Rev. 2013 Jul 23;7:CD007594.
http://www.ncbi.nlm.nih.gov/pubmed/23881659
Sodium Chloride, 0.9%: National Department of Health, Essential Drugs Programme. Medicine review Hydroxyethyl Starch (HES) Solutions for acute hypovolaemia due to blood loss (trauma, intraoperative haemorrhage), 6
October 2015. http://health.gov.za/
iv
Salbutamol respiratory solution: National Department of Health contract circular: HP07-2014DAI. http://health.gov.za/
v
Sodium chloride, 0.9%: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill
patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. http://www.ncbi.nlm.nih.gov/pubmed/23450531
Sodium chloride, 0.9%: Bunn F, Trivedi D. Colloid solutions for fluid resuscitation. Cochrane
Database Syst Rev. 2012 Jul 11;7:CD001319. http://www.ncbi.nlm.nih.gov/pubmed/22786474
Sodium chloride, 0.9%: Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid
therapies: effects on kidney function. Cochrane Database Syst Rev. 2013 Jul 23;7:CD007594.
http://www.ncbi.nlm.nih.gov/pubmed/23881659
Sodium Chloride, 0.9%: National Department of Health, Essential Drugs Programme. Medicine review Hydroxyethyl Starch (HES) Solutions for acute hypovolaemia due to blood loss (trauma, intraoperative haemorrhage), 6
October 2015. http://health.gov.za/
vi
Tranexamic acid, IV: Shakur H et al. Effects of tranexamic acid on death, vascular occlusive events, and
blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.
Lancet. 2010; 376:23-32.
Tranexamic acid: Roberts I et al. The importance of early treatment with tranexamic acid in bleeding trauma
patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011; 377:1096-1101.
Tranexamic acid: Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury.
Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD004896.
vii
Ceftriaxone, IV: Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, Shofer FS, Goyal M. Impact
of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was
initiated
in
the
emergency
department.
Crit
Care
Med.
2010
Apr;38(4):1045-53.
http://www.ncbi.nlm.nih.gov/pubmed/20048677
Ceftriaxone, IV: Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL,
Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman
CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines
Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of
severe
sepsis
and
septic
shock:
2012.
Crit
Care
Med.
2013
Feb;41(2):580-637.
http://www.ncbi.nlm.nih.gov/pubmed/23353941
viii
Dobutamine: MCC registered South African package insert: Pharmaplan Cardiject® powder for IV infusion, 250
mg/vial.
ix
Glyceryl trinitrate, IV: MCC registered South African package insert: AHN Pharma,Nitrocine® injection, 1 mg/mL
x
Sodium chloride, 0.9%: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill
patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. http://www.ncbi.nlm.nih.gov/pubmed/23450531
Sodium chloride, 0.9%: Bunn F, Trivedi D. Colloid solutions for fluid resuscitation. Cochrane
Database Syst Rev. 2012 Jul 11;7:CD001319. http://www.ncbi.nlm.nih.gov/pubmed/22786474
Sodium chloride, 0.9%: Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid
therapies: effects on kidney function. Cochrane Database Syst Rev. 2013 Jul 23;7:CD007594.
http://www.ncbi.nlm.nih.gov/pubmed/23881659
Sodium Chloride, 0.9%: National Department of Health, Essential Drugs Programme. Medicine review Hydroxyethyl Starch (HES) Solutions for acute hypovolaemia due to blood loss (trauma, intraoperative haemorrhage), 6
October 2015. http://health.gov.za/
xi
Burns protocol: PHC STGs and MEL, 2014: http://health.gov.za/
xii
Sodium chloride, 0.9%: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill
patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. http://www.ncbi.nlm.nih.gov/pubmed/23450531
Sodium chloride, 0.9%: Bunn F, Trivedi D. Colloid solutions for fluid resuscitation. Cochrane
Database Syst Rev. 2012 Jul 11;7:CD001319. http://www.ncbi.nlm.nih.gov/pubmed/22786474
2015
20.14
CHAPTER 20
EMERGENCIES AND INJURIES
Sodium chloride, 0.9%: Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid
therapies: effects on kidney function. Cochrane Database Syst Rev. 2013 Jul 23;7:CD007594.
http://www.ncbi.nlm.nih.gov/pubmed/23881659
Sodium Chloride, 0.9%: National Department of Health, Essential Drugs Programme. Medicine review Hydroxyethyl Starch (HES) Solutions for acute hypovolaemia due to blood loss (trauma, intraoperative haemorrhage), 6
October 2015. http://health.gov.za/
xiii
Sodium chloride, 0.9%: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill
patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. http://www.ncbi.nlm.nih.gov/pubmed/23450531
Sodium chloride, 0.9%: Bunn F, Trivedi D. Colloid solutions for fluid resuscitation. Cochrane
Database Syst Rev. 2012 Jul 11;7:CD001319. http://www.ncbi.nlm.nih.gov/pubmed/22786474
Sodium chloride, 0.9%: Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid
therapies: effects on kidney function. Cochrane Database Syst Rev. 2013 Jul 23;7:CD007594.
http://www.ncbi.nlm.nih.gov/pubmed/23881659
Sodium Chloride, 0.9%: National Department of Health, Essential Drugs Programme. Medicine review Hydroxyethyl Starch (HES) Solutions for acute hypovolaemia due to blood loss (trauma, intraoperative haemorrhage), 6
October 2015. http://health.gov.za/
2015
20.15
CHAPTER 21
ONCOLOGY
21.1 MALIGNANCIES
D49.0-D49.9
Certain oncological conditions (e.g. Kaposi sarcoma) may be suitable for
management at secondary level of care, in consultation with a specialist. In
order to facilitate this process at least the following medications should be
available:

Bleomycin

Hydroxyurea

Tamoxifen

Vincristine
This does not preclude procurement of down referred oncology agents
(according to Provincial guidelines) for continuation of care of patients who
have been stabilised.
2015
21.1
CHAPTER 22
MEDICINES USED FOR DIAGNOSIS
22.1 DIAGNOSTIC CONTRAST AGENTS AND RELATED
SUBSTANCES
Medication used in diagnostic radiology includes:

Barium sulphate suspension.

Non-ionic contrast media, e.g.:
o iohexol, or
o iopamidol, or
o iopromide.

Ioversol 300 and 350.
SAFETY
i
The overall rate of adverse reactions is estimated to be less than 1 in 100
when using non-ionic contrast media and serious allergic reactions are even
ii
less common (about 1 in 2000 ). Contrast media-associated fatality is rare,
iii
estimated to be 2 per million injections.
Note: Patients allergic to iodine are at an increased risk of adverse drug
reactions when exposed to iodine-containing contrast media.
Contrast induced nephrotoxicity (CIN)
CIN is variously defined as either a 25% or a 50% rise on pre-contrast
creatinine levels, or an absolute creatinine increase of more than 25
iv, v
micromol/L. CIN is rare in individuals with normal renal function
.
Factors that increase the risk of CIN include: diabetes, pre-existing renal
impairment, age >75 years, anaemia, cardiac failure, hypotension, and the
vi, vii
volume of contrast media injected
.
The probability of developing a 25% rise in creatinine after cardiac
catheterisation in patients given 200 mL of non-ionic contrast media is linked
vii
to co-morbidity :
CIN risk
None
Anaemia
>75 yrs
CCF or low BP
>1 risk factor
No diabetes
eGFR >60
7.5%
7.5%
7.5%
15%
15%
eGFR 40–60
7.5%
15%
15%
15%
15%
eGFR 20–40
7.5%
15%
15%
15%
25%
eGFR <20
15%
15%
25%
25%
25%
2015
22.1
CHAPTER 22
DIAGNOSTICS
Diabetes
eGFR >60
7.5%
15%
15%
15%
25%
eGFR 40–60
15%
15%
15%
25%
25%
eGFR 20–40
15%
25%
25%
25%
25%
eGFR <20
15%
25%
25%
25%
55%
The probability of needing dialysis after cardiac catheterisation correlated with
vii
the risk of CIN :
CIN risk
Dialysis risk
7.5%
0.04%
15%
0.12%
25%
1.1%
55%
13%
Reducing the risk of developing CIN
There is no clear evidence that any specific medication is protective against
the development of CIN. However, meticulous attention to fluid balance is
important in patients at higher risk, as dehydration increases the risk of CIN.
Patients on metformin should be monitored for deterioration in renal function
post procedure as there is a small risk of precipitating lactic acidosis. In high
risk patients it may be advisable to omit metformin for 48 hours after contrast
injection while monitoring serum creatinine.
References:
i
Wang CL, Cohan RH, Ellis JH, Caoili EM, Wang G, Francis IR. Frequency, outcome, and appropriateness of
treatment of nonionic iodinated contrast media reactions. AJR2008; 191:409-415.
http://www.ncbi.nlm.nih.gov/pubmed/18647910
ii
Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and
nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology1990;
175:621-628. http://www.ncbi.nlm.nih.gov/pubmed/2343107
iii
Caro JJ, Trindade E, McGregor M. The risks of death and of severe nonfatal reactions with high- vs lowosmolality contrast media: a meta-analysis. AJR1991;156:825-832. http://www.ncbi.nlm.nih.gov/pubmed/1825900
iv
McDonald JS, McDonald RJ, Comin J, Williamson EE, Katzberg RW, Murad MH, Kallmes DF. Frequency of
acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis.
Radiology. 2013 Apr;267(1):119-28. http://www.ncbi.nlm.nih.gov/pubmed/23319662
v
Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH. Contrast material-induced nephrotoxicity
and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration
rate. Radiology. 2013 Sep;268(3):719-28. http://www.ncbi.nlm.nih.gov/pubmed/23579046
vi
McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J; CIN Consensus Working
Panel. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006 Sep 18;98(6A):27K-36K.
http://www.ncbi.nlm.nih.gov/pubmed/16949378
vii
Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW,
Leon MB, Dangas G. A simple risk score for prediction of contrast-induced nephropathy after percutaneous
coronary intervention: development and initial validation. J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9.
http://www.ncbi.nlm.nih.gov/pubmed/15464318
2015
22.2
CHAPTER 23
SEDATION
23.1 SEDATION
Y47.9
DESCRIPTION
Sedation aims to reduce some combination of anxiety, agitation and pain
while the patient retains control of airway, breathing and blood pressure.
23.1.1 PROCEDURAL SEDATION AND ANALGESIA
Y47.9
Procedural sedation uses medications to allow patients to tolerate
unpleasant medical procedures. It is a brief intervention, unlike sedation in
intensive or palliative care. It is commonly used in emergency units, dentistry
and for certain endoscopic and gynaecological procedures.
GENERAL MEASURES
Procedural sedation is a continuum ranging from minimal sedation
(anxiolysis), moderate sedation, deep sedation, to general anaesthesia.
Deep sedation includes the dissociative state caused by medicines like
ketamine. It is often difficult to predict levels of sedation and therefore
clinicians undertaking procedural sedation should be adequately trained in
this technique. They should have a detailed understanding of the risks and
benefits of the medicines used, and should be competent in resuscitation,
airway management and assisted ventilation.
Procedural sedation should be performed only in an area with adequate light
and space, and fully functional and adequate observation and resuscitation
equipment.
Besides the clinician performing the procedure, there should at least be one
other trained person present responsible for observing the patient, assisting
with resuscitation if necessary and monitoring the patient. The trained
person should observe the patient until the patient is ready for discharge.
Patient monitoring and details of the types and amounts of all medicines
used must be recorded for each procedure, and after the procedure the
patient’s fitness to leave the observation area should be formally assessed
and recorded.
2015
23.1
CHAPTER 23
SEDATION
Sedation level:
Depth
Other aims
Examples
Response
to stimuli
Minimal
Anxiolysis
Sedation
Moderate
Deep
Analgesia
Nitrous oxide
OR
benzodiazepine
Opioid
AND
benzodiazepine
Verbal
Purposefully to
verbal or tactile
Airway
intervention
Not required
Not usually
needed
Breathing
Normal
Usually normal
BP/Pulse
Normal
Monitoring
Intermittent
review of vital
signs
Opioid
AND
benzodiazepine
OR
propofol
OR
etomidate
Purposefully
only after
repeated/painful
May be needed
May need
assistance
Usually normal
Continuous pulse oximetry and
heart rate, intermittent BP and
respiratory rate. Continuous ECG if
CVS disease or sedation with more
than one agent
General
anaesthesia
Unrousable
Often
needed
Often needs
assistance
May need
support
As for any
general
anaesthetic
i
LoE:III
Ketamine
Ketamine administration leads to a dissociative state and provides both
sedation and analgesia. Used on its own, it rarely requires airway
intervention or affects breathing, but may cause hypertension and
tachycardia because of sympathetic stimulation.
ii
LoE:III
MEDICINE TREATMENT
Patient characteristics and required depth and duration of sedation lead to
differences in dosing requirements; the doses listed serve only as a guide,
and incremental further dosing may be required depending on clinical
response.
Minimal sedation and anxiolysis (no analgesic effect required)
Oral sedation may be appropriate for certain procedures.
Initial dose (further dose increments may be necessary – consult full
prescribing information for each agent to determine maximum safe dosages,
and reduce doses in the frail and elderly):

Midazolam, IV, 0.05 mg/kg. (In a 60 kg patient, give boluses of 1 mg
2015
23. 2
CHAPTER 23
SEDATION
every minute; may require up to 3 mg).
iii
OR
LoE:II
Diazepam, IV, 0.1 mg/kg. (In a 60 kg patient, give boluses
of 2 mg every minute; may require up to 10 mg).
OR
Nitrous oxide, inhaled 20 to 50%, in oxygen (will also provide some
analgesia).
Moderate sedation and analgesia
If analgesia is required, one of the above is usually combined with an opiate.
However, ketamine has analgesic activity and can be used on its own, or
combined with a benzodiazepine.
Initial doses:

Fentanyl, IV, 0.25 mcg/kg.
OR
Morphine, IV, 0.1 mg /kg, in increments of 2 mg every 5 minutes.
OR
Ketamine, IV, 0.5 mg/kg (the addition of a benzodiazepine is often
recommended to reduce the incidence/severity of emergence
phenomena such as hallucinations and dreaming, but the benefit of this
is unclear.)
o Repeat doses of 0.5 mg/kg as required, every 5 to 10 minutes.
OR
Nitrous oxide, 20-50% inhaled, in oxygen.
iv
LoE:III
Other agents for moderate sedation
Propofol on its own provides moderate sedation for short procedures (e.g.
endoscopy), but without analgesia:

Propofol, IV, 0.5 mg/kg, repeated as 0.25 mg/kg boluses every 5
v
minutes as required.
LoE:III
Etomidate is a short acting agent like propofol, but is more likely to cause
myoclonus. It has no analgesic effect and is more commonly used for
emergency unit procedures, rather than endoscopies.

Etomidate, IV, 0.1 mg/kg.
o Repeat doses of 0.05 mg/kg every 5 minutes, as required.
vi
LoE:III
Deep sedation and analgesia
This is usually achieved with either higher doses of medications used for
moderate sedation, or by combining an opiate, a benzodiazepine, and either
propofol or etomidate.
When agents are combined, lower doses may be adequate.
2015
23. 3
CHAPTER 23
SEDATION
Supplemental analgesia
Simple analgesics can be given before or after the procedure as appropriate:

Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses
per 24 hours.
o Maximum dose: 15 mg/kg/dose.
o Maximum dose: 4 g in 24 hours.
AND/OR

Ibuprofen, oral, 400 mg 8 hourly with meals after the procedure.
Other routes (e.g. rectal or intramuscular) may be appropriate for certain
indications and medications.
23.1.2 SEDATION IN INTENSIVE CARE
Y47.9
Indications for sedation in intensive care need to be defined for each patient,
and may include one or more of: anxiolysis, analgesia, agitation control, or to
help patients tolerate uncomfortable situations or procedures (e.g. intubation
and ventilation). Sedation requirements fluctuate rapidly and warrant regular
review. Individualised sedation objectives should be clearly defined, and
level of sedation regularly recorded. Sedation protocols that recognise the
need for dose minimisation, weaning and sedation interruptions probably
improve outcomes.
vii
LoE:II
Adequate pain control is often more efficacious than
sedatives for reducing agitation. Delirium should be considered, and
managed appropriately. The doses listed apply to ventilated patients in
whom short term respiratory depression is not a concern.
Short term sedation (less than 24 hours)

Midazolam, IV infusion, 0.05–0.2 mg/kg/hour.
OR
Propofol, IV infusion, 0.5 mg/kg/hour.
viii
LoE:II
Longer term sedation (expected 72 hours or more)

Lorazepam, IV, 0.1 mg/kg/hour.
OR
Midazolam, IV, 0.2 mg/kg/hour.
Note: Lorazepam (0.1 mg/kg/hour) is as effective (and as easy to wean) as
midazolam 0.2 mg/kg/hour) but more difficult to titrate. Due to high fat
solubility, midazolam also becomes ‘long acting’ after infusions of more than
24 hours.
2015
23. 4
CHAPTER 23
SEDATION
Supplemental analgesia:
Analgesia can be added to any of the above regimens:

Morphine, IV infusion, 0.1–0.2 mg/kg/hour.
OR

Fentanyl, IV infusion, 1 mcg/kg/hour (also becomes long acting after
prolonged infusion due to fat solubility.)
ix
LoE:III
23.1.3 SEDATION IN PALLIATIVE CARE
Y47.9
Sedation in palliative care has unique objectives, and tolerance for some
adverse effects may be greater than in other situations. There is also an
emphasis on avoiding parenteral medication. Palliative sedation should be
undertaken by clinicians experienced in the process and the advice of an
expert should be sought where necessary. The aim is to ameliorate
refractory suffering, not to hasten death.
Palliative care medication addresses symptoms such as pain, dyspnoea,
nausea and depression. Managing many of these symptoms involves the
use of medications which may have sedative properties; palliative sedation
involves the additional use of medication where sedation is the primary
objective, and is appropriate only after standard care has proven
unsuccessful.
Dosing in frail, often elderly patients should be titrated to effect.
 Lorazepam, oral, 0.5 mg 4 hourly.
OR
Haloperidol, oral, 0.5 mg 4 hourly.
LoE:III
References:
i
Medication used for sedation: American Society of Anesthesiologists Task Force on Sedation and Analgesia by
Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology.
2002 Apr;96(4):1004-17. http://www.ncbi.nlm.nih.gov/pubmed/11964611
Medication used for sedation: The South African Society of Anaesthesiologists. South African Society of
Anaesthesiologists Sedation Guidelines, 2015. South Afr J Anaesth Analg 2015;21(2)S1-S36.
http://www.sasaweb.com/content/images/SAJAA_V21N2_1665_Sedation_Guideline.pdf
ii
Ketamine: American Society of Anesthesiologists Task Force on Sedation and Analgesia by NonAnesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002
Apr;96(4):1004-17. http://www.ncbi.nlm.nih.gov/pubmed/11964611
iii
Diazepam: Mitchell AR, Chalil S, Boodhoo L, Bordoli G, Patel N, Sulke N. Diazepam or midazolam for external
DC cardioversion (the DORM Study). Europace. 2003 Oct;5(4):391-5.
http://www.ncbi.nlm.nih.gov/pubmed/14753637
Midazolam: Mitchell AR, Chalil S, Boodhoo L, Bordoli G, Patel N, Sulke N. Diazepam or midazolam for external
DC cardioversion (the DORM Study). Europace. 2003 Oct;5(4):391-5.
http://www.ncbi.nlm.nih.gov/pubmed/14753637
iv
Febtanyl IV: Poulos JE, Kalogerinis PT, Caudle JN. Propofol compared with combination propofol or
midazolam/fentanyl for endoscopy in a community setting. AANA J. 2013 Feb;81(1):31-6.
http://www.ncbi.nlm.nih.gov/pubmed/23513321
Morphine, IV: American Society of Anesthesiologists Task Force on Sedation and Analgesia by NonAnesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002
Apr;96(4):1004-17. http://www.ncbi.nlm.nih.gov/pubmed/11964611
2015
23. 5
APPENDIX I
ANTIMICROBIAL MEDICINES
The list of antimicrobial medicines, below, excludes antiretroviral medicines.
It is important to refer to the text of the standard treatment guidelines for detailed
information of specific medicines for specific indications (i.e. duration of therapy, if
used in combination with other antibiotics, prescriber level, etc.).
ACICLOVIR
4.5: Atopic eczema/dermatitis, eczema herpeticum (if patient is unable to swallow
due to odynophagia):

Aciclovir, IV, 5 mg/kg 8 hourly for 7 days.
9.10: Varicella (chickenpox), complicated, 9.11: Zoster (Shingles – with secondary
dissemination or neurological involvement), 14.5.2: Viral meningoencephalitis:

Aciclovir, IV, 10 mg/kg 8 hourly.
9.11: Zoster (Shingles), 18.5.1: Keratitis, herpes simplex:

Aciclovir, ophthalmic ointment 3%, applied into lower conjunctival sac,
five times daily.
9.10: Varicella (chickenpox), complicated, 9.11: Zoster (Shingles), 18.4: Herpes
zoster ophthalmicus:

Aciclovir, oral, 800 mg five times a day or 4 hourly while awake.
4.5: Atopic eczema/dermatitis, eczema herpeticum:

Aciclovir, oral, 400 mg 8 hourly for 7 days.
AMIKACIN
9.1.3: Hospital-Acquired Pneumonia (HAP), 9.1.4: Urinary tract infections,
catheter associated, 10.1.2: Management of selected antiretroviral ADRs - druginduced liver injury:

Amikacin, IV, 15 mg/kg daily.
AMOXICILLIN
6.11: Preterm Labour (PTL) AND Preterm Prelabour Rupture of Membranes
(PPROM), 16.4: Chronic obstructive pulmonary disease (COPD), 17.4: Otitis
media, acute:

Amoxicillin, oral, 500 mg 8 hourly for 5 days.
16.6: Pneumonia, community acquired (uncomplicated):

Amoxicillin, oral, 1 g 8 hourly.
1.1.8: Peptic ulcer, H. pylori +ve:

Amoxicillin, oral, 1 g 12 hourly for 7 days.
3.5: Endocarditis, infective, prophylaxis:

Amoxicillin, oral, 2 g one hour before dental procedure.
2015
AI.1
APPENDIX I
ANTIMICROBIAL MEDICINES
AMOXICILLIN/CLAVULANIC ACID
1.3.8: Bacterial peritonitis, 16.3: Bronchiectasis, 16.4: Chronic obstructive
pulmonary disease (COPD): exposure to amoxicillin last 3 weeks, 8.7.3: Diabetic
foot ulcers, 1.1.2: Diverticulosis, 16.8: Empyema, 17.1: Epiglottitis, 4.7: Leg
ulcers, complicated, 1.2.5: Liver Abscess, pyogenic , 16.5: Lung abscess, 17.4:
Otitis media, acute: not responding to amoxicillin, 5.3: Pelvic Inflammatory
Disease (PID): stage II-IV, 16.7: Pneumonia, aspiration, 16.6: Pneumonia,
community acquired, 6.16: Postpartum Fever, 5.8.4: Septic miscarriage , 19.2:
Snakebites: secondary infection, 7.3.2: Urinary tract infection (UTI): pregnant
women , 6.19.1: Urinary tract infection in pregnancy, 6.19.2: Urinary tract infection
in pregnancy: acute pyelonephritis:

Amoxicillin/clavulanic acid 875/125 mg, oral, 12 hourly.
1.2.7: Acute cholecystitis and acute cholangitis, 1.3.8: Bacterial peritonitis, 8.7.3:
Diabetic foot ulcers: severe infection, 1.1.2: Diverticulosis: cannot take oral
medicines, 16.8: Empyema, 1.2.5: Liver Abscess, pyogenic , 16.5: Lung abscess,
16.7: Pneumonia, aspiration, 6.16: Postpartum Fever, 5.8.4: Septic miscarriage ,
1.1.6: Pancreatitis acute: abscess of the pancreas:

Amoxicillin/clavulanic acid, IV, 1.2 g 8 hourly.
AMPHOTERICIN B
9.1.1: Intravascular catheter infections, candidaemia:

Amphotericin B, IV, 0.7 mg/kg daily.
2.8: Febrile neutropenia, 10.2.4.2: Symptomatic, non-meningeal Cryptococcosis
10.2.4.3: Cryptococcal meningitis: , 14.5.1: Meningitis (cryptococcal meningitis):

Amphotericin B, slow IV infusion, 1 mg/kg daily.
AMPICILLIN
16.6: Pneumonia, community acquired:

Ampicillin, IV, 1 g 6 hourly.
3.5: Endocarditis, infective, prophylaxis, if patient cannot take oral medicines:

Ampicillin, IV/IM, 2 g one hour before dental procedure.
AZITHROMYCIN
3.7: Rheumatic heart disease, prophylaxis of recurrent disease, severe penicillin
allergy:

Azithromycin, oral, 250 mg daily.
16.6: Pneumonia, community acquired (severe pneumonia):

Azithromycin, 500 mg, slow IV (over 3 hours) daily for 3 days.
1.1.8: Peptic ulcer, severe penicillin allergy, 3.7: Rheumatic heart disease, acute
rheumatic fever - severe penicillin allergy, 4.3: Impetigo, 6.11: Preterm Labour
2015
AI.2
APPENDIX I
ANTIMICROBIAL MEDICINES
(PTL) AND Preterm Prelabour Rupture of Membranes (PPROM), severe penicillin
allergy, 10.2.8: Mycobacteriosis - disseminated non tuberculous, 16.4: Chronic
obstructive pulmonary disease (COPD), severe penicillin allergy, 17.1: Epiglottitis,
severe penicillin allergy, 17.4: Otitis media, acute, severe penicillin allergy:

Azithromycin, oral, 500 mg daily for 3 days.
5.3: Pelvic Inflammatory Disease (PID) - stage I, 5.3: Pelvic Inflammatory Disease
(PID), stage II-IV: chlamydia (also for severe penicillin allergy), 5.10: Sexual
Assault (STI prophylaxis), 7.3.4: Prostatitis (acute bacterial prostatitis), 10.4.2:
Non occupational post exposure prophylaxis, sexual assault and inadvertent
exposure:

Azithromycin, oral, 1 g as a single dose.
5.3: Pelvic Inflammatory Disease (PID)-stage I, severe penicillin allergy:

Azithromycin, oral, 2 g as a single dose.
9.8: Tick bite fever, in pregnancy:

Azithromycin, oral, 500 mg 12 hourly for 3 days.
BENZATHINE BENZYLPENICILLIN
3.7: Rheumatic heart disease, prophylaxis,

Benzathine benzylpenicillin (depot formulation), IM, 1.2 million units
every 3–4 weeks.
3.7: Rheumatic heart disease, acute rheumatic fever:

Benzathine benzylpenicillin (depot formulation), IM, 1.2 million units as
a single dose.
6.8: Syphilis, asymptomatic well baby:

Benzathine benzylpenicillin (depot formulation), IM, 50 000 units/kg as a
single dose into the antero-lateral thigh.
6.8: Syphilis, mother:

Benzathine benzylpenicillin (depot formulation), IM, 2.4 million units
weekly for 3 doses.
BENZYL PENICILLIN
6.8: Syphilis, symptomatic baby:

Benzylpenicillin (Penicillin G), IV, 50 000 units/kg, 12 hourly for 10 days.
17.8: Abscess, peritonsillar:

Benzylpenicillin (penicillin G), IV, 2 million units 6 hourly.
9.7: Tetanus:

Benzylpenicillin (penicillin G), IV, 5 MU 6 hourly for 10 days.
3.5: Endocarditis, infective (native valve):

Benzylpenicillin (penicillin G), IV, 5 MU 6 hourly for 4 weeks.
2015
AI.3
APPENDIX I
ANTIMICROBIAL MEDICINES
14.5.1: Meningitis (meningococcal meningitis – confirmed meningococcal disease
only), 14.5.1: Meningitis (pneumococcal meningitis):

Benzylpenicillin (penicillin G), IV, 20 - 24 million units daily in 4–6
divided doses for 10 days.
14.5.3: Meningovascular Syphillis:

Benzylpenicillin (penicillin G), IV, 20 million units daily in 4–6 divided
doses for 10 days.
CEFAZOLIN
11: Cardiac surgery, 11: Gastrointestinal surgery, 11: General surgery, 11:
Neurosurgery , 11: Obstetrics/ gynaecology surgery, 11: Orthopaedic surgery , 11:
Otorhinolaryngology/ Head and neck surgery: severe beta lactam allergy, 11: Plastic
and reconstructive surgery, 11: Thoracic surgery, 11: Urology, 11: Vascular surgery:

Cefazolin, IV, as a single dose.
o If < 80 kg: 1g.
o If ≥ 80 kg: 2 g.
CEFEPIME
2.8: Febrile neutropenia:

Cefepime, IV, 1 g 12 hourly.
CEFTAZIDIME
18.2: Endophthalmitis, bacterial (endogenous endophthalmitis and post-surgical
endophthalmitis):

Ceftazidime, intravitreal, 2.25 mg.
CEFTRIAXONE
10.4.2: Non occupational post exposure prophylaxis, sexual assault and
inadvertent exposure, 5.3: Pelvic Inflammatory Disease (PID), stage I, 7.3.4:
Prostatitis, associated urethritis:5.10: Sexual assault:

Ceftriaxone, IM, 250 mg as a single dose.
1.3.2: Acute inflammatory diarrhoea (dysentery) , 13.2: Arthritis, septic and
osteomyelitis, acute , 1.3.8: Bacterial peritonitis, 17.1: Epiglottitis, 2.8: Febrile
neutropenia, 5.3: Pelvic Inflammatory Disease (PID), stage II-IV, 7.3.2: Urinary
tract infection (UTI), acute pyelonephritis: impaired renal function,6.19.2:
Pyelonephritis, acute, in pregnancy:

Ceftriaxone, IV, 1 g, daily.
14.5.5: Antimicrobial use in patients with head injuries, penetrating brain injuries,
14.5.4: Brain abscess , 9.9: Enteric fever (typhoid), 17.6: Mastoiditis, 14.5.1:
Meningitis, 17.3: Sinusitis, bacterial, complicated:
2015
AI.4
APPENDIX I

ANTIMICROBIAL MEDICINES
Ceftriaxone, IV, 2 g 12 hourly.
16.3: Bronchiectasis, 18.2: Endophthalmitis, bacterial, 9.4: Haemorrhagic fever
syndrome , 16.6: Pneumonia, community acquired, patients >65 years, comorbid
disease, 16.6: Pneumonia, community acquired, severe pneumonia,20.1.4.2:
Septic shock, 9.1.3: Hospital-Acquired Pneumonia (HAP), no risk factors for MDR
infection, 9.1.2: Surgical wound infections: female uro-genital tract, open GIT
surgery:

Ceftriaxone 2 g, IV, daily.
CHLORAMPHENICOL
18.10.2: Eye injury (deep corneal or scleral injuries):

Chloramphenicol 1%, ophthalmic ointment, applied immediately.
18.10.1: Chemical burn, 19.2.2: Venom in the eye:

Chloramphenicol 1%, ophthalmic ointment, applied 6 hourly.
18.1.3: Conjunctivitis, bacterial, 18.10.2: Eye injury (corneal abrasion):

Chloramphenicol 1%, ophthalmic ointment, applied 8 hourly.
11: Ophthalmic surgery:

Chloramphenicol 0.5% ophthalmic drops, instil 1 drop 2–4 hourly for 24
hours prior to surgery.
CIPROFLOXACIN
18.1.3: Conjunctivitis, bacterial, 18.5.2: Keratitis, suppurative:

Ciprofloxacin 0.3%, ophthalmic drops.
14.5.1: Meningitis, nasopharyngeal carriage eradication, 14.5.1: Meningitis,
prophylaxis of contacts, 7.3.3: Recurrent UTI (2-3 infections/year) :

Ciprofloxacin, oral, 500 mg as a single dose.
1.3.1: Cholera:

Ciprofloxacin, oral, 1 g immediately as a single dose.
1.3.2: Acute inflammatory diarrhoea (dysentery) , 1.3.8: Bacterial peritonitis, 9.9:
Enteric fever (typhoid), chronic carriers, 9.9: Enteric fever (typhoid), following
ceftriaxone IV, based on culture sensitivity results,10.2.7: Isosporiasis,
cotrimoxazole allergy, 17.5: Otitis media, chronic, suppurative, 5.3: Pelvic
Inflammatory Disease (PID), stage II-IV: severe penicillin allergy, 7.3.4: Prostatitis,
5.8.4: Septic miscarriage, severe penicillin allergy, following clindamycin IV +
gentamicin IV, 7.3.2: Urinary tract infection (UTI) , 7.3.2: Urinary tract infection
(UTI), acute pyelonephritis: impaired renal function, CrCl <10ml/min, following
ceftriaxone IV, 7.3.2: Urinary tract infection (UTI), acute pyelonephritis: normal
renal function - following gentamicin IV, 9.1.4: Urinary tract infections, catheter
associated:

Ciprofloxacin, oral, 500 mg 12 hourly.
2015
AI.5
APPENDIX I
ANTIMICROBIAL MEDICINES
16.3: Bronchiectasis, pseudomonas infection, 18.2: Endophthalmitis, bacterial,
prophylaxis/soft tissue injury, 17.7.1: Otitis externa, necrostising:

Ciprofloxacin, oral, 750 mg 12 hourly for 7 days.
9.8: Tick bite fever, cannot take oral medicines:

Ciprofloxacin, IV, 400 mg 8 hourly.
CLINDAMYCIN
4.2: Cellulitis and erysipelas, severe penicillin allergy, 4.4: Furuncles and
abscesses, severe penicillin allergy, 5.3: Pelvic Inflammatory Disease (PID), stage
II-IV: severe penicillin allergy, 5.8.4: Septic miscarriage, severe penicillin allergy,
9.1.2: Surgical wound infections, severe penicillin allergy, 17.8: Abscess,
peritonsillar, severe penicillin allergy, 13.2: Arthritis, septic and osteomyelitis,
acute, severe penicillin allergy:

Clindamycin, IV, 600 mg 8 hourly.
3.5: Endocarditis, infective, prophylaxis: severe penicillin allergy (if patient cannot
take oral), 11: Cardiac surgery, severe penicillin allergy, 11: Endoscopic
gastrointestinal procedures: severe penicillin allergy, 11: Gastrointestinal surgery:
severe penicillin allergy, 11: General surgery: severe penicillin allergy, 11:
Neurosurgery: severe penicillin allergy, 11: Obstetrics/ gynaecology surgery:
severe penicillin allergy, 11: Orthopaedic surgery: severe penicillin allergy, 11:
Otorhinolaryngology/Head and neck surgery: severe penicillin allergy, 11: Plastic
and reconstructive surgery: severe penicillin allergy, 11: Thoracic surgery: severe
penicillin allergy, 11: Urology: severe penicillin allergy, 11: Vascular surgery:
severe penicillin allergy:

Clindamycin, IV, 600 mg as a single dose.
3.5: Endocarditis, infective, prophylaxis, severe penicillin allergy:

Clindamycin, oral, 600 mg one hour before the procedure.
8.7.3: Diabetic foot ulcers, severe penicillin allergy:

Clindamycin, oral, 150 mg 8 hourly.
4.5: Atopic eczema/dermatitis: severe penicillin allergy,4.2: Cellulitis and
erysipelas: severe penicillin allergy, 4.4: Furuncles and abscesses: severe
penicillin allergy, 5.3: Pelvic Inflammatory Disease (PID), stage II-IV: severe
penicillin allergy, following gentamicin, IV + clindamycin, IV, 5.8.4: Septic
miscarriage, severe penicillin allergy: following clindamycin IV + gentamicin IV,
9.1.2: Surgical wound infections, severe penicillin allergy, following clindamycin
IV, 9.1.1: Intravascular catheter infections, erythema beyond catheter site, 17.8:
Abscess, peritonsillar, 13.2: Arthritis, septic and osteomyelitis, acute: severe
penicillin allergy:

Clindamycin, oral, 450 mg 8 hourly.
3.5: Endocarditis, infective, prophylaxis, severe penicillin allergy:

Clindamycin, oral, 600 mg one hour before the dental procedure.
2015
AI.6
APPENDIX I
ANTIMICROBIAL MEDICINES
10.2.9: Pneumocystis pneumonia, cotrimoxazole intolerance, unsuccessful
cotrimoxazole desensitisation:

Clindamycin, oral, 600 mg 8 hourly for 21 days.
CLOTRIMAZOLE
4.10: Fungal infections, yeast and dermatophytes:

Clotrimazole 1%, topical, apply 8 hourly until clear of disease (i.e. for at
least 2 weeks after the lesions have cleared).
CLOXACILLIN
4.2: Cellulitis and erysipelas, 4.4: Furuncles and abscesses:

Cloxacillin, IV, 1 g 6 hourly.
13.2: Arthritis, septic and osteomyelitis, acute , 9.1.2: Surgical wound infections:

Cloxacillin, IV, 2 g 6 hourly.
3.5: Endocarditis, infective (native valve):

Cloxacillin, IV, 3 g 6 hourly.
COTRIMOXAZOLE
7.3.3: Recurrent UTI, prophylaxis:

Cotrimoxazole 80/400 mg, oral, 1 tablet at night.
10.2.2: Oppurtunistic infection prophylaxis, with cotrimoxazole, 10.2.7:
Isosporiasis, secondary prophylaxis, 10.2.9: Pneumocystis pneumonia, secondary
prophylaxis, 10.2.10: Cerebral toxoplasmosis, secondary prophylaxis:

Cotrimoxazole, oral, 160/800 daily.
10.2.9: Pneumocystis pneumonia: <60kg, 16.6: Pneumonia,community
acquired,:HIV infected with bilateral diffuse infiltrates on CXR: <60kg:

Cotrimoxazole, oral, 240/1200 6 hourly for 21 days.
10.2.10: Cerebral toxoplasmosis:

Cotrimoxazole 320/1600, oral, 12 hourly for 28 days, followed by 240/1200
tablets 12 hourly for 3 months.
10.2.7: Isosporiasis:

Cotrimoxazole 320/1600, oral, 12 hourly for 10 days.
10.2.9: Pneumocystis pneumonia, >60kg, 16.6: Pneumonia,community
acquired,:HIV infected with bilateral diffuse infiltrates on CXR, >60kg:

Cotrimoxazole 320/1600 mg, oral, 6 hourly for 21 days.
10.2.9: Pneumocystis pneumonia, if vomiting:

Cotrimoxazole, IV, 6 hourly.
o < 60 kg 240/1200 mg.
o > 60 kg 320/ 1600 mg.
2015
AI.7
APPENDIX I
ANTIMICROBIAL MEDICINES
DAPSONE
10.2.9: Pneumocystis pneumonia, if primaquine not available:

Dapsone, oral, 100 mg daily for 21 days.
10.2.9: Pneumocystis pneumonia, secondary prophylaxis, cotrimoxazole
intolerant:

Dapsone, oral, 100 mg daily for at least 6 months.
DOXYCYCLINE
4.1: Acne, inflammatory (moderate):

Doxycycline, oral, 100 mg daily for 3 months.
9.8: Tick bite fever:

Doxycycline, oral, 100 mg 12 hourly for 7 days.
9.3: Brucellosis:

Doxycycline, oral, 100 mg 12 hourly for 6 weeks.
ETHAMBUTOL
16.11.1: INH monoresistant TB:

Ethambutol, oral, 15 mg/kg daily for 6-9 months.
10.2.8: Mycobacteriosis - disseminated non tuberculous:

Ethambutol, oral, 15–20 mg/kg daily.
10.1.2: Management of selected antiretroviral ADRs: drug-induced liver injury:

Ethambutol, oral, 800 - 1200 mg daily.
ETHIONAMIDE
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: <33kg,16.11.2: Multidrugresistant (MDR) TB, continuation phase: <33kg:

Ethionamide, oral, 15–20 mg/kg daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: 33-50kg,16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: 33-50kg:

Ethionamide, oral, 500 mg daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: 50-65kg,16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: 50-65kg:

Ethionamide, oral, 750 mg daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: >65kg,16.11.2: Multidrugresistant (MDR) TB, continuation phase: >65kg:

Ethionamide, oral, 750-1000 mg daily.
2015
AI.8
APPENDIX I
ANTIMICROBIAL MEDICINES
FLUCLOXACILLIN
13.2: Arthritis, septic and osteomyelitis, acute:

Flucloxacillin, oral, 1 g 6 hourly (after 2 weeks of IV cloxacillin therapy
in patients with good clinical response to complete the 4 weeks
treatment).
4.2: Cellulitis and erysipelas, 4.3: Impetigo , 4.4: Furuncles and abscesses, 4.5:
Atopic eczema/dermatitis (infected eczema), 9.1.2: Surgical wound infections ,
9.11: Zoster (Shingles)- if there is suspected associated bacterial cellulitis:

Flucloxacillin, oral, 500 mg 6 hourly.
FLUCONAZOLE
4.10:
Fungal
infections,
dermatophyte
hair
immunocompomised with extensive skin infection,
onychomycosis:

Fluconazole, oral, 200 mg weekly.
and
nail
infections;
4.10: Fungal infections,
10.2.3: Candidiasis of oesophagus/trachea/bronchi, 10.2.4.1: Asymptomatic
cryptococcosis, CrAg positive, maintenance therapy, 10.2.4.2: Symptomatic, NonMeningeal Cryptococcosis, maintenance therapy, 10.2.4.3: Cryptococcal
meningitis, maintenance therapy, 14.5.1: Meningitis, cryptococcal meningitis,
maintenance therapy:

Fluconazole, oral, 200 mg daily.
10.2.3: Candidiasis of oesophagus/trachea/bronchi, if vomiting or unable to
swallow:

Fluconazole, IV, 200 mg daily.
9.1.1: Intravascular catheter infections, candidaemia,10.2.4.1: Asymptomatic
cryptococcosis, CrAg positive, induction therapy , 10.2.4.2: Symptomatic, NonMeningeal Cryptococcosis, induction therapy , 10.2.4.3: Cryptococcal meningitis,
induction therapy , 14.5.1: Meningitis, cryptococcal:

Fluconazole, oral, 800 mg daily
10.2.4.1: Asymptomatic cryptococcosis, CrAg positive, consolidation therapy,
10.2.4.2: Symptomatic, Non-Meningeal Cryptococcosis, consolidation therapy,
10.2.4.3: Cryptococcal meningitis, consolidation therapy:

Fluconazole, oral, 400 mg daily for 8 weeks.
FOSFOMYCIN
6.19.1: Urinary tract infection in pregnancy, severe penicillin allergy, 7.3.2: Urinary
tract infection (UTI) – complicated community acquired cystitis, severe penicillin
st
allergy, 1 trimester:

Fosfomycin 3 g, oral, as a single dose.
2015
AI.9
APPENDIX I
ANTIMICROBIAL MEDICINES
GANCICLOVIR
10.2.6: Cytomegalovirus (CMV), HIV:

Ganciclovir, IV, 5 mg/kg 12 hourly.
18.6: Retinitis, HIV CMV:

Ganciclovir, intravitreal, 2 mg once a week.
GENTAMICIN
3.5: Endocarditis, infective, empiric therapy (prosthetic and native valve);
staphylococcal directed therapy; streptococcal directed therapy (native valve):

Gentamicin, IV, 1.5 mg/kg 12 hourly.
2.8: Febrile neutropenia, 3.5: Endocarditis, infective, 5.3: Pelvic Inflammatory
Disease (PID), stage II-IV: severe penicillin allergy, 5.8.4: Septic miscarriage
(severe penicillin allergy), 6.19.2: Pyelonephritis, acute, in pregnancy, 7.3.2:
Urinary tract infection (UTI), acute pyelonephritis: normal renal function, 11:
Gastrointestinal surgery: severe pencillin allergy, 11: Obstetrics/ gynaecology
surgery: severe penicillin allergy, 11: Urology procedures: severe penicillin allergy:

Gentamicin, IV, 6 mg/kg, daily.
IMIPENEM
2.8: Febrile neutropenia (if fever develops after 48 hours of admission – also
consider local susceptibility patterns):

Imipenem, IV, 500 mg 6 hourly.
9.1.3: Hospital-Acquired Pneumonia (HAP), with risk factors, Ventilator
Associated Pneumonia (VAP):

Imipenem, IV, 1 g 8 hourly (except CNS infections or known epileptics).
ISONIAZID
10.1.2: Management of selected antiretroviral ADRs, drug-induced liver injury,
10.2.1: Isoniazid preventive therapy (IPT):

Isoniazid, oral 300 mg daily.
KANAMYCIN
16.11.2: Multidrug-resistant (MDR) TB, intensive phase, intensive phase: <3365kg:

Kanamycin, IV, 15 mg/kg daily (max: 1 g daily).
16.11.2: Multidrug-resistant (MDR) TB, intensive phase, intensive phase: >65kg:

Kanamycin, IV, 1 g daily.
2015
AI.10
APPENDIX I
ANTIMICROBIAL MEDICINES
LEVOFLOXACIN
10.1.2: Management of selected antiretroviral ADRs, drug-induced liver injury:

Levofloxacin 750 - 1000 mg daily.
MEROPENEM
2.8: Febrile neutropenia:

Meropenem, IV, 1 g 8 hourly.
9.1.3: Hospital-Acquired Pneumonia (HAP), with risk factors, VAP, CNS
infections/seizures:

Meropenem, IV, 2 g 8 hourly.
METRONIDAZOLE
1.3.4: Diarrhoea, antibiotic associated, 6.11: Preterm labour (PTL) and preterm
prelabour rupture of membranes (PPROM) , 14.5.4: Brain abscess:

Metronidazole, oral, 400 mg 8 hourly
5.3: Pelvic Inflammatory Disease (PID), stage I, 1.1.8: Peptic ulcer, H. pylori +ve:

Metronidazole, oral, 400 mg 12 hourly for 7 days.
1.2.6: Liver abscess, amoebic, 1.3.5: Amoebic dysentery:

Metronidazole, oral, 800 mg 8 hourly for 10 days.
1.3.6: Giardiasis, 5.10: Sexual assault , 10.4.2: Non occupational post exposure
prophylaxis, sexual assault and inadvertent exposure:

Metronidazole, oral, 2 g.
11: Gastrointestinal surgery, 11: Obstetrics/ gynaecology surgery, 11:
Orthopaedic surgery , 11: Otorhinolaryngology/ Head and neck surgery, 11:
Urology, 11: Vascular surgery:

Metronidazole, IV, 500 mg, as a single dose.
5.3: Pelvic Inflammatory Disease (PID), stage II-IV, 9.1.2: Surgical wound
infections, female uro-genital tract, open GIT surgery, 9.7: Tetanus , 14.5.4: Brain
abscess , 17.8: Abscess, peritonsillar:

Metronidazole, IV, 500 mg, 8 hourly.
MOXIFLOXACIN
9.1.3: Hospital-Acquired Pneumonia (HAP), severe penicillin allergy, 16.3
Bronchiectasis if pseudomonas infection is suspected, severe penicillin allergy,
16.5: Lung abscess, severe penicillin allergy 16.6: Pneumonia, community
acquired, severe penicillin allergy, 16.7: Pneumonia, aspiration, severe penicillin
allergy, 16.8: Empyema, severe penicillin allergy:

Moxifloxacin, IV, 400 mg daily, until patient apyrexial for 24 hours.
9.1.3: Hospital-Acquired Pneumonia (HAP), severe penicillin allergy, 10.1.2:
Management of selected antiretroviral ADRs, 16.3 Bronchiectasis if pseudomonas
2015
AI.11
APPENDIX I
ANTIMICROBIAL MEDICINES
infection is suspected, severe penicillin allergy, 16.5: Lung abscess, severe
penicillin allergy 16.6: Pneumonia, community acquired, severe penicillin allergy,
16.7: Pneumonia, aspiration, severe penicillin allergy, 16.8: Empyema, severe
penicillin allergy, 16.11.2: Multidrug-resistant (MDR) TB:

Moxifloxacin, oral, 400 mg daily.
NATAMYCIN
18.5.2: Keratitis, suppurative, fungal infection:

Natamycin 5%, ophthalmic drops.
NITROFURANTOIN
7.3.2: Urinary tract infection (UTI) , severe penicillin allergy, 2nd and 3rd trimester:

Nitrofurantoin, oral, 100 mg 12 hourly for 7 days.
7.3.3: Recurrent UTI , prophylaxis

Nitrofurantoin, oral, 100 mg at night for 6 months.
OFLOXACIN
18.1.3: Conjunctivitis, bacterial, 18.5.2: Keratitis, suppurative:

Ofloxacin 0.3%, ophthalmic drops.
PHENOXYMETHYLPENICILLIN
3.7: Rheumatic heart disease, prophylaxis:
 Phenoxymethylpenicillin, oral, 250 mg 12 hourly.
3.7: Rheumatic heart disease, acute rheumatic fever:

Phenoxymethylpenicillin, oral, 500 mg 12 hourly for 10 days.
6.8: Syphilis, penicillin desensitisation:

Phenoxymethylpenicillin, IV, 250 mg/5 mL.
PIPERACILLIN/TAZOBACTAM
2.8: Febrile neutropenia, 9.1.3: Hospital-Acquired Pneumonia (HAP), with risk
factors, Ventilator Associated Pneumonia (VAP), CNS infections/seizures:

Piperacillin/tazobactam, IV, 4.5 g 8 hourly.
PROCAINE PENICILLIN
6.8: Syphilis, symptomatic baby:

Procaine penicillin, IM, 50 000 units/kg daily for 10 days (Not for I.V.
use).
2015
AI.12
APPENDIX I
ANTIMICROBIAL MEDICINES
PYRAZINAMIDE
10.1.2: Management of selected antiretroviral ADRs, drug-induced liver injury,
16.11.1: INH monoresistant TB:

Pyrazinamide, oral, 25 mg/kg daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: <33kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: <33kg:

Pyrazinamide, oral, 30–40 mg/kg daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: 33-50kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: 33-50kg:

Pyrazinamide, oral, 1 g–1750 mg, daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: 50-65kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: 50-65kg:

Pyrazinamide, oral, 1750 mg–2 g, daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: >65kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: >65kg:

Pyrazinamide, oral, 2 g–2 500 mg daily.
RIFABUTIN
10.1: Antiretroviral therapy, TB treatment for patients on ATV/r or darunavir when
rifampicin is contraindicated:

Rifabutin, oral, 150 mg 3 times a week.
RIFAMPICIN
3.5: Endocarditis, infective, 9.3: Brucellosis:

Rifampicin, oral, 7.5 mg/kg 12 hourly for 6 weeks.
16.11.1: INH monoresistant TB:

Rifampicin, oral, 10 mg/kg daily.
10.1.2: Management of selected antiretroviral ADRs, drug-induced liver injury;
<60kg:

Rifampicin, oral 450 mg daily.
10.1.2: Management of selected antiretroviral ADRs, drug-induced liver injury:

Rifampicin, oral 600 mg daily.
14.5.1: Meningitis, severe penicillin allergy:

Rifampicin, oral, 600 mg 12 hourly.
RIFAMPICIN/ISONIAZID
16.9: Tuberculosis, pulmonary, continuation phase: 30-37kg, 16.10:
Tuberculosis, pleural, continuation phase: 30-37kg:

Rifampicin/isoniazid, oral, 300/150 mg, daily for 4 months.
2015
AI.13
APPENDIX I
ANTIMICROBIAL MEDICINES
16.9: Tuberculosis, pulmonary, continuation phase: 38-54kg, 16.10: Tuberculosis,
Pleural, continuation phase: 38-54kg:

Rifampicin/isoniazid, oral, 450/225 mg, daily for 4 months.
16.9: Tuberculosis, pulmonary, continuation phase: >55kg16.10: Tuberculosis,
Pleural, continuation phase: >55kg:

Rifampicin/isoniazid, oral, 600/300 mg, daily for 4 months.
RIFAMPICIN/ISONIAZID/PYRAZINAMIDE/ETHAMBUTOL
16.9: Tuberculosis, pulmonary, initial phase: 30-37kg, 16.10: Tuberculosis,
Pleural, initial phase: 30-37kg:

Rifampicin/isoniazid/pyrazinamide/ethambutol, oral, 300/150/800/500
mg, daily for 2 months.
16.9: Tuberculosis, pulmonary, initial phase: 38-54kg:16.10: Tuberculosis, Pleural,
initial phase: 38-54kg:

Rifampicin/isoniazid/pyrazinamide/ethambutol, oral, 450/225/1200/825
mg, daily for 2 months.
16.9: Tuberculosis, pulmonary, initial phase:55-70kg, 16.10: Tuberculosis, Pleural,
initial phase:55-70kg:

Rifampicin/isoniazid/pyrazinamide/ethambutol, oral, 600/300/1600/1100
mg, daily for 2 months.
16.9: Tuberculosis, pulmonary, initial phase:71kg and over, 16.10: Tuberculosis,
Pleural, initial phase:71kg and over,

Rifampicin/isoniazid/pyrazinamide/ethambutol, oral, 750/3755/2000/1375
mg, daily for 2 months.
TENOFOVIR
1.2.4.2: Hepatitis B, chronic (non-HIV co-infection):

Tenofovir, oral, 300 mg daily.
TERIZIDONE
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: <33kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: <33kg:

Terizidone, oral, 15–20 mg/kg, daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: 33-65kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: 33-65kg:

Terizidone, oral, 750 mg, daily.
16.11.2: Multidrug-resistant (MDR) TB, intensive phase: >65kg, 16.11.2:
Multidrug-resistant (MDR) TB, continuation phase: >65kg:

Terizidone, oral, 750 mg – 1000 mg, daily.
2015
AI.14
APPENDIX I
ANTIMICROBIAL MEDICINES
VALGANCICLOVIR
10.2.6 Cytomegalovirus (CMV) - Biopsy-proven GIT disease and pneumonitis:

Valganciclovir, oral, 900 mg 12 hourly for the first 3 weeks, if available.
Maintenance treatment is not indicated unless there has been a relapse.
10.2.6 Cytomegalovirus (CMV) – CNS disease:

Initial treatment: Valganciclovir, oral, 900 mg 12 hourly for the first 3
weeks, if available.

Maintenance treatment: Valganciclovir, oral, 900 mg daily until CD4
count rises to > 100 on ART.
18.6 Retinitis, HIV CMV (Limited CMV retinitis):

Valganciclovir, oral, 900 mg 12 hourly for the first 3 weeks, then 900 mg
daily until immune recovery (CD4 > 100) and a minimum of 3 months of
therapy with valganciclovir (if available).
VANCOMYCIN
1.3.4: Diarrhoea, antibiotic-associated (failure to respond to metronidazole after 5
days):

Vancomycin, oral, 125 mg 6 hourly. (Give the parenteral formulation
orally).
18.2: Endophthalmitis, bacterial:

Vancomycin, intravitreal, 1 mg.
3.5: Endocarditis, infective:

Vancomycin, IV, 20 mg/kg 12 hourly.
2.8: Febrile neutropenia, IV, skin infection, 9.1.1: Intravascular catheter infections,
S. aureus infection, 9.1.2: Surgical wound infections, MRSA, 14.5.1: Meningitis,
severe penicillin allergy:

Vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20 mg/kg/dose
12 hourly.
2015
AI.15
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
AMIKACIN, IV
 Amikacin, IV, 15 mg/kg (if BMI is > 40 use ideal body weight + 40% of the
difference between ideal and actual body weight), daily. In severe sepsis
or septic shock a loading dose of 25 mg/kg should be given (irrespective
of renal function).
o If eGFR is 40–60 ml/min, adjust maintenance dose to 15 mg/kg
every 36 hours (check trough amikacin level and give the next dose
when level < 5 mg/L).
o Maximum daily dose 1.5 g for a maximum of 10 days.
o Amikacin is potentially nephrotoxic and ototoxic – monitor creatinine
three times per week, as well as pre-dose amikacin trough levels;
and discontinue if vestibular or cochlear symptoms develop.
o Therapeutic drug monitoring: pre-dose amikacin trough levels. Aim
for a trough level of < 5 mg/L.
 Normal renal function: do not wait for the amikacin level before
giving the next dose. The level should be used to adjust the dose
for the next day if applicable.
 Impaired renal function: wait for the amikacin level and give the
next dose when level < 5 mg/L.
 In obese patients also measure peak concentrations (immediately
after infusion).
AMIODARONE, ORAL
 Amiodarone, oral, 800 mg daily for 7 days.
o
o
o
o
o
Then 600 mg daily for 3 days.
Hypotension may occur, especially during the loading dose phase
Titrate to maintenance dose of 200–400 mg daily.
May cause hypothyroidism or thyrotoxicosis - monitor thyroid
function every 6 months.
Monitor for pulmonary symptoms; and perform baseline CXR before
starting long term therapy and annually thereafter, to monitor for
interstitial pulmonary fibrosis.
AMOXICILLIN/CLAVULANIC ACID, ORAL
o
o
2015
875/125 mg tablets containing 875mg amoxicillin trihydrate and
125mg clavulanic acid.
Dosage recommendation: amoxicillin/clavulanic acid, 875/125 mg
oral, 12 hourly.
o When treating pneumonia in areas where there is a
confirmed high level of penicillin intermediate resistant
Streptococcus pneumoniae (>/= 5%):
o ADD: Amoxicillin 1 000 mg, oral, daily between the
amoxicillin/clavulanic acid doses (i.e. 8 hours after the
morning dose of amoxicillin/clavulanic acid).
AII.1
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
AMOXICILLIN/CLAVULANICACID,IV

Amoxicillin/clavulanic acid IV is not suitable for intramuscular or
subcutaneous administration.

Amoxicillin/claculanic acid, 1.2 g powder vials for intravenous injection
containing amoxicillin sodium equivalent to 1 g of amoxicillin and
potassium clavulanate equivalent to 200 mg clavulanic acid.
o Dosage Recommendation: Amoxicillin/clavulanic acid, 1.2 g, IV, 8
hourly.
o Directions for use:
Powder vials for injection can be reconstituted by dissolving in
20 mL water for injection.
For intravenous infusion, the reconstituted vial should be further
diluted with the desired volume of a suitable infusion fluid (e.g.
Sodium chloride 0.9%, 100 mL).
Reconstituted vials can be administered intravenously by
injection over 2 minutes or slow intravenous infusion over
30 minutes.
The contents of the vials must be used within 20 minutes and
thereafter any unused material discarded.
o Precautions:
- Allergy to penicillins.
- Drug-induced cholestatic hepatitis may occur, typically a few
weeks after starting therapy. Used with caution in patients with
evidence of hepatic dysfunction.
- Dosage adjustments required in renal impairment:
» Creatinine clearance > 70 ml/min = no dose adjustment
required.
» Creatinine clearance 10–30 ml/min = 1.2 g as a single dose
followed by 600 mg 12 hourly.
» Creatinine clearance < 10 ml/min = 1.2 g as a single dose
followed by 600 mg daily.
AMPHOTERICN B, IV

Amphotericin B, IV, 1 mg/kg daily.
o Ensure adequate hydration to minimise the risk of nephrotoxicity.
o Monitoring
- Serum potassium and creatinine (baseline and twice weekly).
Monitoring of serum potassium and creatinine should occur
more frequently in neutropenic patients (3 times a week).
- Monitor haemoglobin (baseline and weekly).
- Careful attention to fluid monitoring of intake and output, and
daily weight.
2015
AII.2
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
AMPHOTERICN B, IV (continued)
o
Management
- If significant hypokalaemia (K < 3.3 mmol/L):

Increase potassium supplementation i.e. potassium chloride
(KCL) 40 mmoL diluted in sodium chloride 0.9%, 1000 mL, at a
rate of 125 mL/hour, IV, and repeat serum potassium in 24
hours.
OR

Potassium chloride, oral, 600–1200 mg 8 hourly.
o Monitor potassium daily.
-
If hypokalaemia remains uncorrected, check serum magnesium
and correct as required.
-
If creatinine increases by ≥ 2 fold from baseline value, either
temporary omit an amphotericin B dose, or increase prehydration to 1 litre 8 hourly.

Once improved, restart at 0.7 mg/kg daily and consider
alternate day amphotericin B.

If creatinine remains elevated i.e. ≥ 2 fold from baseline
value, discontinue amphotericin B and continue with
fluconazole, oral, 800 mg daily (for fungal infections known
to be responsive to fluconazole e.g Cryptococcus).
(Adapted from: WHO. Rapid advice: diagnosis, prevention and management of cryptococcal
disease in HIV-infected adults, adolescents and children: Prevention, monitoring and
management of amphotericin B toxicity. 2011 [Online] [Accessed March 2016]
http://www.ncbi.nlm.nih.gov/books/NBK299520/pdf/Bookshelf_NBK299520.pdf
CLINDAMYCIN, IV
 Clindamycin IV, 600 mg.
»
»
»
Dilute the contents of the vial in 100 mL of diluent prior to infusion.
Infuse over 20 minutes.
Note: Rapid infusion can cause flushing, pain, thrombophlebitis,
hypotension and cardiopulmonary arrest.
DIGOXIN, ORAL
 Digoxin, oral, 0.125 mg daily, adjust according to rate response, if in atrial
fibrillation, and trough plasma level.
o Digoxin trough plasma levels (before the morning dose) should be
maintained between 0.6-1 nmol/L. Monitor after 7 days and
periodically thereafter.
o Patients at high risk of digoxin toxicity are:
 the elderly,
 patients with renal dysfunction,
 hypokalaemia, and
 patients with low lean body mass.
2015
AII.3
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
LABETALOL, IV
 Labetalol, IV infusion, 2 mg/minute to a total of 1–2 mg/kg.
o
o
o
o
Initial dose: 2 mg/minute
Titrate to response up to 300 mg total cumulative dose (e.g.
discontinue after 2.5 hours of 2 mg/minute).
Usual total dose required is 50–200 mg (1–2 mg/kg).
Follow with an oral antihypertensive regimen.
LITHIUM, ORAL

Lithium, oral, 250 mg 12 hourly.
o Usual dose range: 200–500 mg/dose 12 hourly.
o May be given as a single total daily dose at night to improve adherence.
o Monitor trough (pre-dose) plasma levels after 5 days.
o Lithium has a narrow therapeutic window. The therapeutic range is
0.4–0.8 mmol/L for maintenance therapy, and 0.8–1.0 mmol/L in
mania.
o If levels are sub-therapeutic and the patient is adherent increase the
daily dose by 250 mg and repeat trough plasma levels after 5 days.
o Maintain therapeutic blood levels of lithium for as long as the patient
is on lithium. Monitor lithium levels and renal function at least
monthly for the first 3 months of therapy.
o Monitor lithium levels 6 monthly once stable levels have been
achieved, together with serum creatinine, sodium and potassium.
o Check TSH (for lithium-induced hypothyroidism) and serum calcium
(for lithium-induced hyperparathyroidism) before starting treatment
and annually thereafter.
o Beware of combining lithium with ACE-inhibitors, NSAIDs and
thiazide diuretics, as they all potentiate the risk for lithium toxicity.
METFORMIN, ORAL
Metformin, oral, 500 mg twice daily with meals.
o Titrate dose slowly depending on HbA1c and/or fasting blood glucose
levels to a maximum dose of 850 mg 8 hourly.
o Monitor renal function.
o Dose-adjust in renal impairment as follows:
- eGFR > 60 mL/min:
Normal daily dose (see above).
- eGFR < 60 mL/min:
Half of the daily dose.
- eGFR < 30 mL/min:
Stop metformin.
o Contra-indicated in:
- renal impairment i.e. eGFR < 30 mL/min,
- uncontrolled congestive cardiac failure,
- severe liver disease,
- patients with significant respiratory compromise, or
- peri-operative cases.
2015
AII.4
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
MORPHINE, IV

Morphine, IV, to a total maximum dose of 10 mg.
o Morphine, IV, 3–5 mg as a single dose then further boluses of 1–2
mg/minute and monitor closely.
o Dilute 10 mg up to 10 mL with sodium chloride 0.9%.
o Total maximum dose: 10 mg.
o Repeat after 4 hours if necessary.
o Monitor response to pain and effects on respiration and blood
pressure.
PHENYTOIN, IV

Phenytoin, IV, 20 mg/kg diluted in sodium chloride 0.9% (not dextrose)
administered not faster than 50 mg/minute, with cardiac monitoring.
o Mixing instructions: For preparation of the infusion, the contents of a
vial of phenytoin should be well mixed in 0.9% sodium chloride at a
concentration of less than 4 g/L and be completely administered
within 1 hour of mixing to avoid precipitation.
o Cardiac monitoring should be done during the infusion.
o If dysrhythmias occur, interrupt the infusion temporarily and
reintroduce slowly, once rhythm becomes stable.
o Continue with, IV, 5 mg/kg/day (300 mg daily for most adults).
POTASSIUM CHLORIDE, IV
 Must always be diluted before infusion.

Potassium chloride, IV, diluted in 1 L sodium chloride 0.9%.
o Rapid infusion of potassium chloride can cause fatal dysrhythmias.
o Infusion rates > 20 mmol/hour are very irritable to peripheral veins.
o Potassium chloride 15% for intravenous use contains 20 mmol K+
per 10 mL ampoule.
o Potassium chloride infusion – see diabetes section for the
administration of potassium infusion in DKA (Section 8.6.2: Diabetic
ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS)).
o Non DKA; Dilute potassium chloride in a non glucose containing
solution (e.g. 0.9% sodium chloride) to a concentration not
exceeding 40 mmol/L. Maximum rate of infusion should not exceed
20 mmol/ hour.
o As large volumes of solution may need to be given, monitor the
patient for fluid overload.
o For preparation of the infusion, the contents of an ampoule of
potassium chloride should be well mixed in 0.9% sodium chloride.
o An example prescription might be: ‘dilute 40 mmol KCl (two 10 ml
ampoules of the 15% solution containing 20mmol KCl/ampoule) in 1
litre of 0.9% sodium chloride, and mix thoroughly. Infuse at a rate of
125 ml/hour, and repeat 8 hourly (i.e. give three litres of the solution
2015
AII.5
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
containing 40 mmol KCl per litre as a constant infusion over a 24
hour period)’.
VANCOMYCIN, IV

Vancomycin, IV, 30 mg/kg as a loading dose. Follow with 20 mg/kg/dose
12 hourly. Duration depends on the organism & site of infection: for
methicillin-resistant Staphylococcus aureus duration is 2 weeks after first
negative blood culture, or 4 weeks for complicated infections (e.g.
endocarditis).
o The rate of infusion should not exceed 1g/hour (i.e. at least 2 hours
for a 2 g infusion).
o Note: Rapid infusion can cause flushing, pain, thrombophlebitis,
hypotension and cardiopulmonary arrest.
o Weigh patients and estimate eGFR (see chapter 7: Nephrological/
urological disorders).
o See table for dosing interval and measurement of trough
concentrations.
o Aim for trough concentration of 10–20 mcg/mL except in osteitis or
endocarditis or if MIC > 1 when trough should be 15–20 mcg/mL.
o If trough is too low, increase dose (specialist consultation if unsure
how much to increase) and/or shorten dose interval to 8 hourly.
o If trough too high increase dosing interval (specialist consultation if
unsure how much to increase).
o Vancomycin is not significantly removed by conventional intermittent
haemodialysis. Dosing and monitoring as for those with eGFR < 25
mL/min.
Dosing intervals and when to measure trough concentrations of vancomycin:
eGFR (mL/min)
Dosing interval
(hours)
Measurement
concentrations
>80
12
Before 3rd dose
50-79
24
Before 3rd dose
35-49
36
Before 2nd dose
25-34
<25
or
haemodialysis
or
CAPD
48
Before 2nd dose
When
level <15
trough
of
trough
3 days after loading dose
(Adapted with permission from Groote Schuur hospital’s protocol).
2015
AII.6
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
WARFARIN, oral
 Warfarin, oral, 5 mg daily adjusted to maintain INR between 2 and 3.
o
Warfarin interactions:
A large number of medicines interact with warfarin leading to underor over-anticoagulation, and careful evaluation of all new medicines,
herbal and over-the counter products is critical. This includes (but is
not an exhaustive list):
- Medicines altering platelet function e.g. NSAIDs, aspirin,
clopidogrel, etc.
- Food or medicines altering vitamin K synthesis e.g. antibiotics.
- Medicines interfering with warfarin metabolism e.g. efavirenz,
rifampicin, macrolide antibiotics, simvastatin, cimetidine,
phenytoin, carbamazepine, etc.
- Grapefruit juice.
Unless INR is widely out of range the modest adjustments recorded below
should be followed:
INITIATION
Warfarin initiation dosing protocol (week 1) with INR target: 2–3
Day therapy
Day 1
INR Value
2 to 3 days after
initiation
< 1.5
(2.5 mg daily for high sensitivity)
5–7.5 mg daily
1.5 – 1.9
2.5–5 mg daily
2.0 – 2.5
2.5 mg daily
> 2.5
< 1.5
Hold warfarin and recheck INR next day
7.5–10 mg daily
1.5 – 1.9
5–10 mg daily
2.0 – 3.0
2.5–5 mg daily
> 3.0
Hold warfarin and recheck INR in1–2 days
2 to 3 days after
last INR check
Total daily dose
5 mg daily
Frequency of INR monitoring after initiation of warfarin
Check INR
Every 2–3 days
Then every week
Then every 2 weeks
Then every 4 weeks
2015
Until INR within therapeutic range on 2 consecutive INR checks
Until INR within therapeutic range on 2 consecutive INR checks
Until INR within therapeutic range on 2 consecutive INR checks
When dose is stable, check monthly
AII.7
APPENDIX II
PRESCRIBING INFORMATION FOR SPECIFIC MEDICINES
MAINTENANCE
Warfarin maintenance dosing protocol to maintain an INR 2-3:
INR<1.5
INR:1.51.9
Extra Dose. Increase
weekly
Increase
dose 5%.
weekly
dose 10%.
INR:2.03.0
INR:3.14.0
INR:4.1-5
INR:5.19.0
INR>9
.0
No
change.
Decrease
weekly
dose 5%.
Withhold 1
dose.
*Withold 2
doses.
Admit.
Decrease
weekly
dose 10%.
Decrease
weekly
dose 20%.
*History and examination to exclude bleeding. Admit persons with additional risks for bleeding.
Frequency of INR monitoring for maintenance of warfarin
Check INR
Every 3–5 days
If start/stop interacting medication, change in diet,
change in activity level or other change that could
affect INR.
Every 1–2 weeks
If dose needed adjustment by 5–10%.
Every 4 weeks
If maintained on same stable dose < 6 months.
Every 6–8 weeks
If maintained on same stable dose ≥ 6 months.
2015
AII.8
GUIDELINES FOR THE MOTIVATION OF A NEW MEDICINE
ON THE NATIONAL ESSENTIAL MEDICINES LIST
Section 1: Medication details
» Generic name.
A fundamental principle of the Essential Drug Programme is that of generic
prescribing. Most clinical trails are conducted using the generic name.
» Proposed indication.
» There will usually be many registered indications for the medication. However,
this section should be limited to the main indication which is supported by the
evidence provided in section 2.
» Prevalence of the condition in South Africa
» This information is not always readily available. However, it is an important
consideration in the review of a proposed essential medicine.
» Prescriber level.
» Here the proposed prescriber level should be included. If more than one level
is proposed each relevant box should be ticked.
Section 2: Evidence and motivation
» Estimated benefit:
 Effect measure: this is the clinical outcome that was reported in the clinical
trial such as BP, FEV, CD4, VL etc.
 Risk benefit: this should reported in the clinical trial and, in most cases,
includes the 95% confidence level (95% CI). Absolute risk reduction, also
termed risk difference, is the difference between the absolute risk of an
event in the intervention group and the absolute risk in the control group.
 Number Need to Treat (NNT): gives the number of patients who need to be
treated for a certain period of time to prevent one event. It is the recipr ocal
of the absolute risk or can be calculated using the formula below.
Calculations
Intervention group
Control group
Measure
Absolute risk:
Number needed to treat
Bad outcome
a
b
Equation
Good outcome
c
d
Total patients
a+c
b+d
[b/(b+d)] – [a/(a+c)]
1
[b/(b+d)] – [a/(a+c)]
Relative risk
[a/(a+c)] ÷ [b/(b+d)]
Odds ratio
[a/(a+c)] ÷ [c/(a+c)]
[b/(b+d)] ÷ [d/(b+d)]
Reference - Aust Prescr 2008;31:12–16)
xxxvii
= (a/c) ÷ (b/d)
»
Motivating information (Level of evidence based on the SORT system):
 The National Essential Medicine List Committee has endorsed the
adoption of the SORT system for categorising levels of evidence. This
1
system contains only three levels:
Level I
Good quality evidence
Systematic review of RCTs with
consistent findings
High quality individual RCT
Level II
Limited
quality
patient Systematic review of lower quality
orientated evidence
studies or studies with inconsistent
findings
Low quality clinical trial
Cohort studies
Case-control studies
Level III
Other
Consensus guidelines, extrapolations
from bench research, usual practice,
opinion, disease-oriented
evidence (intermediate or physiologic
outcomes only), or case series
A: Newer product: for most newer products, level 1 evidence such as high
quality systematic reviews or peer-reviewed high quality randomised
controlled trials should be identified and referenced in the space provided.
B: Older products: many of these products were developed prior to the wide
use of randomised controlled trials. However, there may be level 1 evidence
where the product was used as the control arm for a newer product. If no level
1 evidence can be identified, then level II data from poorer quality controlled
trials or high quality observational studies should be referenced in the space
provided.
»
Cost considerations:
 Where a published reference supporting the review of cost is available
comments should be made regarding its applicability to the South African
public sector environment.
 Possible unpublished information that can be included:
o Cost per daily dose or course of therapy – for long term or chronic
therapy such as hypertension the usual daily dose should be
calculated (Dose x number of times a day) and converted into the
number of dosing units e.g. tablets. This is then used to calculate the
cost per day. For medications used in a course of therapy such as
antibiotics this is then multiplied by the number of days in the course
of therapy.
1
Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a
patient-centered approach to grading evidence in the medical literature. Am Fam Physician.
2004;69:550-6.
xxxviii
o
o
Cost minimisation is used where there is evidence to support
equivalence and aims to identify the least costly treatment by
identifying all the relevant costs associated with the treatment.
Cost-effectiveness analysis is used to compare treatment
alternatives that differ in the degree of success in terms of the
therapeutic or clinical outcome. By calculating a summary
measurement of efficiency (a cost-effectiveness ratio), alternatives
with different costs, efficacy rates, and safety rates can be fairly
compared along a level playing field.
Where any of these have been performed tick the relevant block and send as an
attachment with all the calculations. If possible, the spread sheet should be
supplied electronically.
Section 3: Motivator’s Details
The receipt of all submission will be acknowledged. In addition, all decisions with
supporting arguments will be communicated where appropriate. This section
therefore forms a vital link between the motivator and the decision making
process.
xxxix
Motivation form for the inclusion of a new
medication
on the National Essential Medicines List
Section 1: Medication details
Generic name (or International Nonproprietary Name):
Proposed indication:
Prevalence of condition (based on epidemiological data, if any):
Prescriber level
Primary Health Care
Medical Officer
Specialist
1
2
3
Designated Specialist
4
Section 2: Evidence and motivation
2.1 Estimated benefit
Effect measure
Risk difference (95% CI)
NNT
2.2: Motivating information (Level of evidence based on the SORT system)
A. Newer product: High quality systematic reviews or peer-reviewed high quality randomised
controlled trials (Level I)
Author
Title
Journal ref
B. Older product with weaker evidence base: Poorer quality controlled trials or high quality
observational studies (Level II)
Author
Title
Journal ref
2.3: Cost-considerations
Have you worked up the cost?
YES
Daily cost
Cost minimisation
Other relevant cost information if available:
Author
Title
Journal ref
2.4: Additional motivating comments.
Section 3: Motivator’s Details
PTC Title:
NO
Cost-effectiveness analysis
Date submitted:
GUIDELINES FOR ADVERSE DRUG REACTION REPORTING
National Pharmacovigilance Programme
The Medicines Control Council (MCC) has a responsibility to ensure the safety, efficacy
and quality of all medicines used by the South African public. The National
Pharmacovigilance Programme is coordinated by the MCC and has a dedicated Unit,
The National Adverse Drug Event Monitoring Centre (NADEMC), in Cape Town, which
monitors the safety of all registered medicines in South Africa.
What is Pharmacovigilance?
Pharmacovigilance is defined as the science and activities concerned with the
detection, assessment, understanding and prevention of adverse reactions to
medicines (i.e. adverse drug reactions or ADRs). The ultimate goal of this activity is to
improve the safe and rational use of medicines, thereby improving patient care and
public health.
What is an Adverse Drug Reaction (ADR)?
The Medicines Control Council (MCC) defines an Adverse Drug Reaction (ADR) as a
response to a medicine which is noxious and unintended, including lack of efficacy, and
which occurs at any dosage and can also result from overdose, misuse or abuse of a
medicine.
Who should report Adverse Drug Reactions?
All health care workers, including doctors, dentists, pharmacists, nurses and other
health professionals are encouraged to report all suspected adverse reactions to
medicines (including vaccines, X-ray contrast media, traditional and herbal remedies),
especially when the reaction is not in the package insert, potentially serious or clinically
significant.
xli
What happens to a report?
All ADR reports are entered into a national ADR database. Each report is evaluated to
assess the causal relationship between the event and the medicine. A well-completed
adverse drug reaction/product quality form submitted could result in any of the
following:
»
additional investigations into the use of the medicine in South Africa;
»
educational initiatives to improve the safe use of the medicine;
»
appropriate package insert changes to include the potential for the reaction, and
»
changes in the scheduling or manufacture of the medicine to make it safer.
The purpose of ADR reporting is to reduce the risks associated with the use of
medicines and to ultimately improve patient care.
Will reporting have any negative consequences on the health worker or the
patient?
An adverse drug reaction report does not constitute an admission of liability or that the
health professional contributed to the event in any way. The outcome of a report,
together with any important or relevant information relating to the reaction, will be sent
back to the reporter as appropriate. The details of a report are stored in a confidential
database. The names of the reporter or any other health professionals named on a
report and that of the patient will be removed before any details about a specific
adverse drug reaction are used or communicated to others. The information is only
meant to improve the understanding of the medicines used in the country.
Is the event possibly an ADR?
The following factors should be considered when an adverse drug reaction is
suspected:
1.
What exactly is the nature of the reaction? (Describe the reaction as clearly as
possible and where possible provide an accurate diagnosis.)
xlii
2.
Did the reaction occur within a reasonable time relationship to starting treatment
with the suspected medicine? (Some reactions occur immediately after
administration of a medicine while others take time to develop.)
3.
Is the reaction known to occur with the particular medicine as stated in the
package insert or other reference? (If the reaction is not documented in the
package insert, it does not mean that the reaction cannot occur with that particular
medicine.)
4.
Did the patient recover when the suspected medicine was stopped? (Some
reactions can cause permanent damage, but most reactions are reversible if the
medication is stopped.)
5.
Did the patient take the medicine again after the reaction abated (i.e. rechallenge).
If so, did the same reaction occur again? (In most situations it is not possible or
ethical to rechallenge the patient with the same medicine. If such information is
available or if such a rechallenge is necessary, recurrence of the event is a strong
indicator that the medicine may be responsible.)
6.
Can this reaction be explained by other causes (e.g. underlying disease/s; other
medicine/s; toxins or foods)? (It is essential that the patient is thoroughly
investigated to decide what the actual cause of any new medical problem is. A
medicine-related cause should be considered, when other causes do not explain
the patient’s condition.)
What types of reactions should be reported?
The following adverse drug reactions should be reported:

All ADRs to newly marketed drugs or new drugs added to the EDL

All serious reactions and interactions

ADRs that are not clearly stated in the package insert.

All adverse reactions or poisonings to traditional or herbal remedies
Report even if you are not certain that the medicine caused the event.
xliii
What Product Quality Problems should be reported?
The following product quality problems should be reported:

suspected contamination;

questionable stability;

defective components;

poor packaging or labeling;

therapeutic failures.
How can ADRs be prevented from occurring?
Some ADRs are unavoidable and cannot be prevented. However, most ADRs can be
prevented by following the basic principles of rational use of medicines.
How are adverse drug reactions reported?
An Adverse Drug Reaction/Product Quality Report Form is enclosed in this book and
should be completed in as much detail as possible before returning it by fax or post to
any of the addresses provided below. Additional forms can be obtained by contacting
the MCC at these addresses. Report forms may also be accessed via the following
website: http://www.mccza.com
1. The Registrar of Medicines
Medicines Control Council, Department of Health, Private Bag X828
Pretoria, 0001
Tel: (021) 395 8003/8176; Fax: (012) 395 8468
2. The National Adverse Drug Event Monitoring Centre (NADEMC)
C/o Division of Pharmacology, University of Cape Town,
Observatory, 7925
(021) 447 1618; Fax: (021) 448 6181
xliv
Adverse drug reaction
ARF 1
ADVERSE DRUG REACTION AND PRODUCT QUALITY PROBLEM
REPORT FORM
(Identities of reporter and patient will remain strictly confidential)
NATIONAL ADVERSE DRUG
EVENT MONITORING CENTRE
NADEMC
The Registrar of Medicines
Private Bag X 828
Pretoria 0001
In collaboration with the WHO
International Drug Monitoring
Programme
PATIENT INFORMATION
Name (or initials): .........................................................
Patient Reference Number: ……………………………………………..
Sex:
M F Age:
DOB:
Weight
Height (cm)
(kg)
............
..... / ....../ ........
..............
..............
ADVERSE REACTION/PRODUCT QUALITY PROBLEM (tick appropriate
box)
Adverse
reaction
and/or Product
Quality problem
Date of onset of reaction:
........./........../............
Time of onset of reaction:
….........hour.............min
Description of reaction or problem (Include relevant tests/lab data,
including dates):
1. MEDICINES / VACCINES / DEVICES (include all concomitant
medicines)
Trade Name and
Daily
Route
Date
Date
Reasons
Batch No.
Dosage
Started Stopped
for use
(Asterisk
Suspected
Product)
ADVERSE REACTION OUTCOME (Check all that apply)
death
life-threatening
disability
hospitalisation
congenital anomaly
Other................
required intervention to
prevent permanent
impairment/damage
Reaction abated after stopping medicine:
Y
N
Event reappeared on rechallenge:
Y
N
Rechallenge
not done
Recovered:
Y
N
Y
N
Sequelae:
Describe Sequelae:.......................
Adverse drug reaction
ARF 1
COMMENTS: (e.g. Relevant history, Allergies, Previous exposure, Baseline
test results/lab data)
2. PRODUCT QUALITY PROBLEM:
Trade
Name
Batch
No
Registration
No
Product available for evaluation?:
Dosage
form &
strength
Y
Expiry
Date
Size/Type
of
container
N
REPORTING HEALTHCARE PROFESSIONAL:
NAME: .................................................................................
QUALIFICATIONS:.................................................................
ADDRESS: ...............................................................................
...............................................................................Postal Code: ……………
TEL: (............)......................................................
……………….…………..
Signature
…………………..
Date
This report does not constitute an admission that medical personnel or
the product caused or contributed to the event.
ADVICE ABOUT VOLUNTARY REPORTING
Report adverse experiences with:

medications (drugs, vaccines and biologicals)

medical devices (including in-vitro diagnostics)

complementary / alternative medicines (including
traditional, herbal remedies, etc)
Report even if:

you're not certain the product caused the event

you don't have all the details
Please report especially:

adverse drug reactions to newly marketed products

serious reactions and interactions with all products

adverse drug reactions which are not clearly
reflected in the package insert.
Investigational Products and Product Quality Problems:

fax: (012) 395-9201

phone: (012) 395-9341
Report Product Quality Problems such as:

suspected contamination

questionable stability

defective components

poor packaging or labelling

therapeutic failures
Important numbers:
Adverse Events Following Immunisation:

fax: (012) 395 8905

phone: (012) 395 8914/5
Confidentiality: Identities of the reporter and patient will remain strictly confidential.
Your support of the Medicine Control Council’s adverse drug reaction monitoring programme is much appreciated.
Information supplied by you will contribute to the improvement of medicine safety and therapy in South Africa.
PLEASE USE ADDRESS PROVIDED BELOW - JUST FOLD IN THIRDS, TAPE and MAIL
_____________________________________________________________________________
No
Postage
stamp
necessary if posted in the
Republic of South Africa
Geen posseël nodig nie
indien in die Republiek van
Suid-Afrika gepos
Postage will be paid
by the Addressee
Posgeld sal deur die
geadresseerde
betaal word
BUSINESS REPLY SERVICE
BESIGHEIDSANTWOORDDIENS
Free Mail Number:
BNT 178
Vryposnommer:
DEPARTMENT OF HEALTH
DEPARTEMENT VAN GESONDHEID
REGISTRAR OF MEDICINES
REGISTRATEUR VAN MEDISYNE
PRIVATE BAG / PRIVAATSAK X828
PRETORIA
0001
DISEASE NOTIFICATION PROCEDURES
The disease reporting system in South Africa is based on government law (the Health Act,
Act No. 61 of 2003), together with regulations on the reporting of specific diseases to the
Local, Provincial and/or National Health Department.
Who should notify
The first health care professional to come into contact with a patient presenting with one
of the prescribed Notifiable Medical Conditions is required by law to notify. This may
include clinic personnel, infection control nurses, other hospital staff or private medical
practitioners. In the event of deaths (or cases) in the community, a member of the
community is obliged to notify the event.
Which diseases to notify
Currently 33 broad medical conditions are currently notifiable in South Africa (see List of
Notifiable Medical Condition). Some conditions (e.g. tuberculosis and viral hepatitis) have
been divided into various components, resulting in more than 40 notifiable medical
conditions.
Notifiable medical conditions have been sub-divided into two categories according to type
of disease:
a) Category A: these are medical conditions that require immediate notification to the
regional/provincial or national Department of Health by telephone or fax upon initial
diagnosis (presumptive or confirmed) with written notification form (GW17/5) to follow
within five days.
Any health care professional identifying even a single case of a disease (presumptive or
laboratory confirmed) contained in the Category A should make an immediate notification
directly to the designated local health officer through fax or telephonically as rapidly as
possible (within 24 hours). The local health officer must report to the Provincial health
officer and/or to the National Department of Health. Where it is applicable, laboratory
confirmation should be obtained at the earliest opportunity and also reported to the
designated health office. After reporting through a telephone/fax, it is still required of the
health care provider to send a complete GW17/5 form to the designated local health
authority within five days after telephonic reporting.
b) Category B: these are medical conditions that require written notification (GW17/5
form) only, within seven days of diagnosis.
The notification system is based on clinical notifications and, therefore, all suspected
cases of a notifiable condition must be notified immediately.
xlix
Reporting a Notifiable Disease during an outbreak
During an outbreak of a notifiable disease, report all cases by phone, email or fax. Daily
reporting by health facilities should be maintained through an Outbreak Case Line Listing
Form as well through the notification form (GW17/5) to the local health authority that must
report to the provincial health officials and the National Department of Health.
Priority Reporting of MDR & XDR-TB
Tuberculosis (TB) is one of 33 medical conditions, which is notifiable in terms of the
National Health Act (Act 61 of 2003). The Directorate: Epidemiology and Surveillance
have instituted a priority reporting for MDR and XDR TB. This means that all health care
facilities, public and private, including clinics, hospitals, laboratories, general practitioners
and private specialist doctors, are required to report all cases of MDR and XDR TB to the
Department of Health within 24 hours.
How to notify
The initial notification of a medical condition is done on a case-based form (GW 17/5) with
the relevant details by the health personnel e.g., clinic personnel, infection control nurses,
other hospital staff, public or private medical practitioners. Initial notification makes tracing
as easy as possible, since a disease notification demands action (follow-up) at the
peripheral level.
The GW17/5 form makes provision for the notification of cases as well as deaths. Any
person contracting a notifiable disease and then dies from the disease should be notified
twice: first as a “CASE” and then later as a “DEATH”. This will ensure that when
estimating the “Case Fatality Rate” (CFR%), all deaths in the numerator are also
included in the denominator. Depending on the structural organization of the province, the
completed GW 17/5 forms is sent to the relevant local health authority, district health
office or the provincial office.
National Department of Health
Cluster: Health Information, Evaluation & Research (HIER)
Directorate: Epidemiology & Surveillance
Private Bag X828
PRETORIA
0001
Tel: 012 395 8150/1
l
List of Notifiable Medical Conditions
Category A: Immediate notification (within 24 hours) of diagnosis by the health care
professional (telephone or fax) to the designated district or provincial health officer.
Acute flaccid paralysis
Anthrax
Cholera
Crimean-Congo haemorrhagic fever
Other haemorrhagic fevers of Africa
Food poisoning
Measles
Meningococcal infection
Plague
Rabies, human
Yellow fever
Category B
Brucellosis
Congenital syphilis
Diphtheria
Haemophilus Influenza type B
Lead poisoning
Legionellosis
Leprosy
Malaria
Paratyphoid fever
Poisoning agricultural stock remedies
Poliomyelitis
Rheumatic fever
Tetanus
Tetanus neonatorum
Trachoma
Tuberculosis primary
Tuberculosis pulmonary
Tuberculosis of other respiratory organs
Tuberculosis of meninges
Tuberculosis of intestines, peritoneum
Tuberculosis of bones and joints
Tuberculosis of genito-urinary system
Tuberculosis of other organs
Tuberculosis miliary
Typhoid fever
Typhus fever (lice-borne)
Typhus fever (ratflea-borne)
Viral hepatitis type A (acute)
Viral hepatitis type B (acute)
Viral hepatitis non-A non-B (acute)
Viral hepatitis unspecified
Whooping cough
li
INDEX OF DISEASE CONDITIONS
Abscess, peritonsillar
Acid aspiration prophylaxis
Acne
Acquired coagulation defects
Acromegaly
Acute cholecystitis and acute cholangitis
Acute coronary syndromes
Acute inflammatory diarrhoea (dysentery)
Acute kidney injury
Acute liver failure
Acute myelopathy
Acute pain due to gastrointestinal colic
Acute spinal cord injury
Acute stress disorder and post-traumatic stress disorder
Adrenal insufficiency (Addison disease)
Adult vaccination
Aggressive disruptive behaviour in adults
Alcohol withdrawal delirium (Delirium tremens)
Amenorrhoea
Amitraz poisoning
Amoebic dysentery
Anaemia
Anaemia in pregnancy
Anaemia, aplastic
Anaemia, chronic disorder
Anaemia, haemolytic
Anaemia, iron deficiency
Anaemia, megaloblastic
Anaemia, sickle cell
Anaesthesia-related acute hypertension
Anaesthetic-related acute hypotension
Analgesia for acute non-surgical pain
Analgesia for chronic cancer pain
Analgesia for chronic neuropathic pain
Analgesia for chronic non-cancer pain
Analgesic poisoning
Anaphylaxis/anaphylactic shock
Androgen deficiency
Angina pectoris, stable
Angioedema
Anterior hypopituitarism
Anticoagulant poisoning
Anticoagulants and spinal or epidural blocks
Antimicrobial stewardship
Antimicrobial use in patients with head injuries
Antiretroviral agents poisoning
Antiretroviral therapy
Arthritis, reactive
Arthritis, rheumatoid (RA)
Arthritis, septic and osteomyelitis, acute
lii
17.6
12.12
4.1
2.17
8.1
1.14
3.4
1.15
7.8
1.8
14.24
12.19
14.4
15.12
8.1
9.6
15.1
15.17
5.5
19.27
1.17
2.1
6.1
2.6
2.5
2.5
2.1
2.3
2.7
12.10
12.9
12.18
12.17
12.18
12.16
19.12
20.2
8.3
3.9
20.1
8.25
19.29
12.12
9.1
14.20
19.21
10.1
13.10
13.1
13.4
INDEX OF DISEASE CONDITIONS
Asthma, acute
Asthma, chronic persistent
Asymptomatic cryptococcosis, CrAg positive
Atherosclerotic peripheral arterial disease
Atopic eczema/ dermatitis
Atrial fibrillation
Atrial flutter
AV junctional re-entry tachycardias
Bacterial peritonitis
Benign prostatic hyperplasia
Benzodiazepine poisoning
Benzodiazepine withdrawal
Bipolar disorder
Bleeding disorders
Boomslang snake bite
Bowel preparations
Brain abscess
Brain oedema due to traumatic injury
Brain oedema due to tumours and inflammation
Bronchiectasis
Brucellosis
Burns
Calcium channel blocker poisoning
Candidiasis of oesophagus/trachea/bronchi
Cannabis withdrawal
Carbon monoxide poisoning
Cardiac arrest – cardiopulmonary resuscitation
Cardiac arrest adults
Cardiac dysrhythmias
Cardiogenic shock
Cellulitis and erysipelas
Cerebral toxoplasmosis
Cerebrovascular disease
Chemical burn (of the eye(s))
Cholera
Chorea
Chronic hypertension (in pregnancy)
Chronic kidney disease (CKD)
Chronic management of STEMI/NSTEMI/UA
Chronic obstructive pulmonary disease (COPD)
Cluster headache
Cocaine poisoning
Complications of diabetes
Confusional states/delirium
Congestive Cardiac Failure (CCF)
Conjunctivitis
Conjunctivitis, adenoviral
Conjunctivitis, allergic
Conjunctivitis, bacterial
Cotrimoxazole poisoning
Cryptococcal meningitis
liii
16.1
16.2
10.17
3.10
4.5
3.12
3.15
3.15
1.18
7.18
19.19
15.21
15.4
2.10
19.6
1.1
14.19
14.26
14.25
16.5
9.8
20.8
19.20
10.16
15.21
19.31
20.11
20.12
3.11
20.5
4.2
10.24
14.1
18.10
1.15
14.22
6.11
7.1
3.9
16.7
14.12
19.22
8.16
15.3
3.21
18.1
18.1
18.2
18.2
19.21
10.19
INDEX OF DISEASE CONDITIONS
Cryptococcosis
Cryptosporidiosis diarrhoea
Crystalloids
Cushing syndrome
Cystitis
Cytomegalovirus (CMV)
Dehydration/ketosis in labour
Dementia
Depolarising muscle relaxants
Depressive disorder, major
Diabetes insipidus (Posterior hypopituitarism)
Diabetes mellitus
Diabetes mellitus in pregnancy
Diabetic emergencies
Diabetic foot ulcers
Diabetic ketoacidosis (DKA) and hyperosmolar nonketotic diabetic coma
(HONK)
Diabetic kidney disease
Diabetic neuropathies
Diagnostic contrast agents and related substances
Diarrhoea
Diarrhoea, acute non-inflammatory
Diarrhoea, antibiotic-associated
Discontinuation symptoms of serotonin reuptake inhibitors
Disseminated Intravascular Coagulation (DIC)
Distributive shock
Diverticulosis
Drug-resistant TB
Dry eye
Dyslipidaemia
Dysmenorrhoea
Ear, nose and throat disorders
Emergencies
Empyema
Endocarditis, infective
Endometriosis
Endophthalmitis, bacterial
Enteric fever (typhoid)
Envenomation
Epidural anaesthesia
Epiglottitis
Epilepsy
Erectile dysfunction
Erythema Multiforme, Stevens Johnson Syndrome, Toxic Epidermal
Necrolysis
Essential tremor
Ethanol poisoning
Ethylene glycol poisoning
Examples of ward prescriptions for postoperative analgesia according to
anticipated pain severity
Exposure to poisonous substances
liv
10.17
10.20
12.8
8.4
6.24
10.21
6.21
14.5
12.2
15.8
8.26
8.4
6.2
8.11
8.17
8.13
8.17
8.16
22.1
1.15
1.16
1.17
15.23
2.17
20.3
1.1
16.18
18.9
8.18
5.1
17.1
20.1
16.14
3.24
5.5
18.3
9.15
19.1
12.13
17.1
14.6
7.19
4.7
14.22
19.25
19.26
12.7
19.10
INDEX OF DISEASE CONDITIONS
Eye disorders
Eye injury: blunt/penetrating/foreign body
Febrile neutropenia
Fungal infections
Furuncles and abscesses
Gastrointestinal disorders
Gastro-Oesophageal Reflux Disease (GORD)
General anaesthesia
Generalised anxiety disorder
Gestation, 1st trimester (< 13 weeks)
Gestation, second trimester (13 to 20 weeks)
Giardiasis
Glaucoma
Glomerular disease and nephritic syndrome
Gout
Graves’ hyperthyroidism
Haematuria
Haemophilia A and B, Von Willebrand disease
Haemorrhagic fever syndrome
Headache and facial pain syndromes
Healthcare-associated infections
Heart block (second or third degree)
Heart disease in pregnancy
Heavy metal poisoning
Hepatic disorders
Hepatitis B, acute
Hepatitis B, chronic (HIV coinfection)
Hepatitis B, chronic (non-HIV coinfection)
Hepatitis, non-viral
Hepatitis, viral
Herpes zoster ophthalmicus
Hiatus hernia
Hirsutism and virilisation
HIV in kidney disease
HIV in pregnancy
Hospital-acquired pneumonia (HAP)
Hydatid disease
Hydrocarbon poisoning
Hypercalcaemia, including primary hyperparathyroidism
Hyperemesis gravidarum
Hyperkalaemia
Hypernatraemia
Hypertension
Hypertension, asymptomatic severe
Hypertensive crisis, hypertensive emergency
Hypertensive disorders in pregnancy
Hypertensive urgency
Hyperthyroidism
Hypocalcaemia
Hypoglycaemia
Hypokalaemia
lv
18.1
18.10
2.8
4.13
4.4
1.1
1.2
12.1
15.10
5.11
5.12
1.18
18.4
7.6
13.7
8.3
7.14
2.11
9.9
14.11
9.1
3.20
6.4
19.32
1.7
1.10
1.13
1.11
1.7
1.10
18.6
1.3
5.6
10.6
6.11
9.4
9.10
19.24
8.20
6.16
7.9
7.11
3.27
3.32
3.33
6.7
3.32
8.29
8.21
8.11
7.10
INDEX OF DISEASE CONDITIONS
Hyponatraemia
Hypothyroidism
Hypovolaemic shock
Idiopathic intracranial hypertension (Pseudotumour cerebri)
Immune reconstitution inflammatory syndrome (IRIS)
Immune Thrombocytopenia (ITP)
Impetigo
Incomplete miscarriage in the first trimester
Induction (inhalation anaesthesia)
Infectious and parasitic conditions
Infertility
Inflammatory bowel disease
Ingestion of caustic substances
INH monoresistant TB
Injuries
Insect bites and stings
Insomnia
Intravascular catheter infections
Intravenous analgesics
Intravenous fluids
Iron poisoning
Ischaemic heart disease and atherosclerosis, prevention
Isoniazid poisoning
Isoniazid preventive therapy (IPT)
Isosporiasis
Jaundice in pregnancy
Kaposi sarcoma (KS)
Keratitis
Keratitis, herpes simplex
Keratitis, suppurative
Labour induction
Labour pain, severe
Leg ulcers, complicated
Lithium poisoning
Liver abscess, amoebic
Liver abscess, pyogenic
Local anaesthetic toxicity
Lung abscess
Maintenance (inhalation anaesthesia)
Major electrolyte abnormalities
Malaria
Malaria, non-severe
Malaria, severe
Malignancies
Malignant hyperthermia
Management of selected antiretroviral adverse drug reactions
Mastoiditis
Medical conditions associated with severe pain
Medical management of eye injury
Medicines to reverse muscle relaxation
Medicines to treat complications of anaesthesia
lvi
7.11
8.22
20.3
14.14
10.14
2.14
4.3
5.8
12.2
14.15
5.6
1.3
19.25
16.18
20.8
19.1
15.22
9.2
12.5
12.8
19.17
3.1
19.20
10.15
10.22
6.15
10.25
18.6
18.6
18.7
6.18
6.20
4.9
19.19
1.14
1.13
12.9
16.11
12.2
7.9
9.11
9.11
9.12
21.1
12.9
10.7
17.5
12.18
18.10
12.4
12.9
INDEX OF DISEASE CONDITIONS
Medicines used for diagnosis
Meningitis
Meningovascular syphilis
Menopause and perimenopausal syndrome
Methanol poisoning
Methaqualone withdrawal
Midtrimester miscarriage (from 13–22 weeks gestation)
Migraine
Miscarriage
Movement disorders
Multidrug-resistant TB
Multiple sclerosis
Muscle relaxants
Muscle relaxation for rapid sequence intubation
Myasthenia gravis
Mycobacteriosis – disseminated non-tuberculous
Myelodysplastic syndromes
Narrow QRS complex (supraventricular) tachydysrhythmias
Nephrotic syndrome
Neurocysticercosis
Neurogenic shock
Neurological disorders
Neuropathy
Non occupational post exposure prophylaxis, sexual assault and inadvertent
exposure
Non-depolarising muscle relaxants (NDMRs)
Non-ST Elevation Myocardial Infarction (NSTEMI) and Unstable Angina (UA)
Non-Sustained (< 30 Seconds) irregular wide QRS tachycardias
Nutritional support
Obsessive-compulsive disorder
Obstructive shock
Oedema, cerebral
Opiate withdrawal,e.g. heroin
Opioid poisoning
Opportunistic diseases
Oppurtunistic infection prophylaxis, with cotrimoxazole
Oral analgesics
Organophosphate poisoning
Osteo-arthritis
Osteomalacia/Rickets
Osteoporosis
Otitis externa
Otitis externa, necrotising
Otitis media, acute
Otitis media, chronic, suppurative
Overactive bladder
Paget disease
Pain, chronic
Pancreatitis, acute
Pancreatitis, chronic
Panic disorder
lvii
22.1
14.15
14.19
5.14
19.27
15.20
5.8
14.11
5.7
14.20
16.19
14.25
12.2
12.3
14.25
10.22
2.10
3.11
7.7
14.20
20.3
14.1
14.23
10.29
12.3
3.7
3.18
12.19
15.11
20.6
14.25
15.18
19.14
10.15
10.16
12.5
19.28
13.5
8.24
8.23
17.5
17.5
17.3
17.4
7.19
8.24
12.15
1.3
1.4
15.11
INDEX OF DISEASE CONDITIONS
Papular urticaria
Paracetamol poisoning
Paraquat poisoning
Parkinsonism
Pelvic Inflammatory Disease (PID)
Peptic ulcer
Perioperative analgesia
Perioperative analgesics
Peripheral nerve block or wound infiltration
Persistent depressive disorder (Dysthymic disorder)
Pesticides and rodenticides
Phaeochromocytoma
Pituitary disorders
Pneumocystis pneumonia
Pneumonia, aspiration
Pneumonia, community acquired
Poisoning
Poisoning with amphetamine derivatives
Poisoning with substances that cause methaemoglobinaemia
Portal hypertension and cirrhosis
Post-exposure prophylaxis
Post-exposure prophylaxis, occupational
Postoperative analgesia ward prescriptions
Postoperative nausea and vomiting (PONV)
Postoperative pain in the recovery room
Postpartum fever
Postpartum haemorrhage
Premedication
Preterm labour (PTL) and preterm prelabour rupture of membranes
(PPROM)
Prevention of PONV
Primary aldosteronism
Procedural sedation and analgesia
Prolactinoma
Prostatitis
Psoriasis
Psychiatric disorders
Psychosis, acute
Pulmonary oedema, acute
Pyelonephritis, acute
Rabies vaccination
Recurrent UTI
Regular wide QRS tachycardias
Renal calculi
Renal replacement therapy
Retinitis, HIV CMV
Rheumatic heart disease
Rhinitis, allergic, persistent
Salicylate poisoning
Schizophrenia
Scorpion envenomation
lviii
4.12
19.12
19.29
14.21
5.3
1.5
12.4
12.5
12.14
15.9
19.27
8.27
8.25
10.23
16.14
16.11
19.1
19.23
19.32
1.9
10.26
10.26
12.7
12.10
12.6
6.21
6.22
12.1
6.16
12.10
8.28
23.1
8.25
7.18
4.10
15.1
15.14
20.6
6.24
9.6
7.17
3.17
7.2
7.9
18.7
3.34
17.2
19.14
15.14
19.7
INDEX OF DISEASE CONDITIONS
Sedation
Sedation in intensive care
Sedation in palliative care
Sedative hypnotic poisoning
Septic miscarriage
Septic shock
Seronegative spondylarthritis
Severe pre-eclampsia and eclampsia
Sexual assault
Shingles (Herpes zoster)
Silent miscarriage or early fetal death
Single toxic nodules
Sinus arrest
Sinus bradycardia
Sinusitis, bacterial, complicated
Snakebites
Spider envenomation
Spinal (intrathecal) anaesthesia
ST Elevation Myocardial Infarction (STEMI)
Status epilepticus
Stimulant withdrawal, including cocaine and methamphetamines
Stroke
Subarachnoid haemorrhage
Suppression of labour for fetal distress
Surgical and diagnostic products
Surgical antibiotic prophylaxis
Surgical wound infections
Sustained (> 30 Seconds) irregular wide QRS tachycardias
Symptomatic, non-meningeal cryptococcosis
Syphilis
Systemic and Healthcare-Associated infections
Systemic lupus erythematosus (SLE)
Tension headache
Termination of pregnancy (TOP)
Tetanus
The Rhesus-negative woman
Theophylline poisoning
Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic Syndrome (TTPHUS)
Thyroid crisis
Thyroiditis
Tick bite fever
Topical anaesthesia
Torsades de pointes ventricular tachycardia (VT)
Toxic multinodular goiter
Transient ischaemic attach (TIA)
Treatment of adverse effects of chronic opiod use
Treatment of PONV
Tricyclic antidepressant poisoning
Trigeminal neuralgia
Trophoblastic neoplasia (‘Hydatidiform mole’)
lix
23.1
23.4
23.5
19.19
5.9
20.5
13.9
6.9
5.13
4.14
5.7
8.31
3.21
3.21
17.2
19.2
19.8
12.12
3.4
14.10
15.20
14.1
14.4
6.18
18.8
11.1
9.3
3.18
10.19
6.14
9.1
13.10
14.13
5.10
9.14
6.23
19.18
2.16
8.32
8.31
9.15
12.14
3.19
8.31
14.3
12.17
12.11
19.15
14.13
5.10
INDEX OF DISEASE CONDITIONS
Tuberculosis, pleural (TB pleurisy)
Tuberculosis, pulmonary
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Typhoid
Urinary incontinence
Urinary tract infection (UTI)
Urinary tract infection (UTI) in pregnancy
Urinary tract infections, catheter associated
Urology section
Urticaria
Uterine bleeding, abnormal
Uveitis
Varicella (Chickenpox), complicated
Venom in the eye
Venous thrombo-embolism
Vertigo, acute
Viral infections
Viral meningoencephalitis
Viral warts/anogenital warts
Wide QRS (ventricular) tachyarrhythmias
Withdrawal from substances of abuse
Zoster (Shingles)
lx
16.17
16.15
8.9
8.6
1.18
5.14
7.15
6.24
9.5
7.14
4.11
5.1
18.8
9.16
19.6
2.18
17.7
4.14
14.18
4.14
3.17
15.16
9.17
INDEX OF MEDICINES
Abacavir
Abacavir/lamivudine/efavirenz
Abacavir/lamivudine/nevirapine
Acetazolamide
Acetic acid 2% in alcohol
Acetylcholine chloride
Acetylcysteine
Aciclovir, parenteral
Aciclovir, oral
Aciclovir, opthalmic ointment
ACTH Depot
Activated charcoal
Adenosine
Adrenaline (epinephrine), parenteral
Adrenaline (epinephrine), inhalation
Albendazole
Albumin
Alendronate
Alfacalcidol
Alfentanil
Allopurinol
Aluminium hydroxide BP
Amikacin
Amiodarone, oral
Amiodarone, parenteral
Amitriptyline
Amlodipine
Amoxicillin
Amoxicillin/clavulanic acid, parenteral
Amoxicillin/clavulanic acid, oral
Amphotericin B
Ampicillin
Anti-D immunoglobulin
Aqueous cream BP
Artemether/lumefantrine
Artesunate
Ascorbic acid, parenteral
Aspirin
Atazanavir/ritonavir
Atenolol
Atorvastatin
6.13, 10.4
10.2
10.2
14.14, 18.5
17.4
18.9
19.12, 19.13, 19.14, 19.33
4.7, 9.17, 14.18
4.7, 9.17, 18.6
9.17, 18.7
8.2
19.11, 19.12, 19.14, 19.16, 19.18, 19.29
3.16
3.19, 3.20, 12.9, 19.5, 20.1, 20.2, 20.4,
20.5, 20.13
17.1
9.10, 14.20
1.9, 1.10
8.23
8.21
12.10
13.8
7.5
9.4, 9.5, 10.11, 10.13. 10.21
3.14, 3.17, 3.18
3.17, 3.18
8.16, 9.18, 12.18, 13.3, 13.6, 14.12, 14.14,
14.23, 14.24, 15.9, 18.6
3.10, 3.30, 3.32, 6.8, 7.7, 8.28, 13.11, 14.2
1.6, 3.27, 6.17, 16.9, 16.12, 17.3
1.14, 1.15, 1.18, 1.2, 1.4, 5.9, 6.22, 8.18,
16.11, 16.13, 16.14, 16.15,
1.14, 1.15, 1.18, 1.2, 4.10, 5.4, 5.9, 6.22,
6.24, 6.25, 7.15, 8.17, 16.11, 16.13, 16.14,
16.15, 16.5, 16.6, 16.9, 17.1, 17.3, 17.6,
19.3
2.9, 9.3, 10.19, 10.20, 14.17
3.27, 16.12
5.9, 5.13, 6.23
4.6
9.12, 9.13
9.13
19.33
3.4, 3.7, 3.11, 3.9, 6.9, 8.9, 13.11, 14.2,
14.3
10.3, 10.5, 10.27
3.6, 3.8, 3.10, 3.13, 3.14, 3.16, 3.30, 3.33,
8.30. 8.31, 8.32
10.7
lxi
INDEX OF MEDICINES
Atropine, parenteral
Atropine, opthalmic drops
Azathioprine
Azithromycin, oral
Azithromycin, parenteral
Barium sulphate
Beclometasone, inhaler
Benzathine benzylpenicillin
Benzoyl peroxide
Benzylpenicillin (Penicillin G)
Betamethasone, topical
Betamethasone, topical scalp lotion
Betamethasone, parenteral
Betamethasone, oral
Betaxolol, ophthalmic drops
Bezafibrate
Bimatoprost, ophthalmic drops
Biperiden, parenteral
Bloemycin
Boomslang antivenom
Brimonidine, ophthalmic drops
Bromocriptine
Budesonide, nasal spray
Bupivacaine
Bupivacaine, dextrose
Calcitriol
Calcium carbonate
Calcium elemental
Calcium gluconate, parenteral
Carbamazepine
Carbimazole
Carbopol gel
Carvedilol
Cefazolin
Cefepime
Ceftazidime, intravitreal
Ceftriaxone
Cetirizine
Chloramphenicol, ophthalmic drops
Chloramphenicol, ophthalmic ointment
Chlorhexidine, in water
Chloroquine sulphate (as base)
Chlorphenamine
Chlorpromazine
Ciprofloxacin, oral
3.20, 3.21, 12.4, 19.21, 19.28, 19.29
18.8, 18.11
1.7, 13.11
1.6, 3.34, 3.35, 4.4, 5.4, 5.5, 5.14, 6.17,
7.18, 9.15, 10.23, 10.30, 13.10, 16.9, 17.1,
17.3,
16.13
22.1
16.4
3.34, 3.35, 6.14, 6.15
4.1
3.25, 6.15, 9.14, 14.16, 14.19, 17.6
4.6, 4.11, 4.12
4.11
6.17, 14.26
14.26
18.4
8.19, 10.7
18.5
12.11, 14.22, 15.2
21.1
19.6
18.5
8.25
17.2
12.12, 12.14
12.12
7.6
6.9, 7.5
8.21, 8.23
1.4, 6.10, 7.8, 8.21, 19.8, 19.9, 19.21
8.17, 12.18, 14.12, 14.13, 14.23, 14.24,
14.7, 15.7
8.30, 8.32
18.9
1.10, 3.13, 3.14, 3.23, 3.90
11.1, 11.2, 11.3
2.9
18.3
1.16, 1.19, 2.9, 5.4, 5.14, 6.25, 7.16, 7.18,
9.4, 9.9, 9.16, 10.30, 13.5, 13.10, 14.15,
14.16, 14.19, 14.20, 16.6, 16.13, 17.1,
17.3, 17.5, 18.3, 20.5
4.12, 17.2, 17.3, 18.2, 20.2, 20.3
11.4
18.2, 18.10, 18.11, 19.7
19.3
13.1, 13.2, 13.11
4.7, 4.13
15.2, 15.15, 19.23
1.15, 1.16, 1.19, 5.4, 5.9, 7.15, 7.16, 7.17,
lxii
INDEX OF MEDICINES
Ciprofloxacin, parenteral
Ciprofloxacin, ophthalmic drops
Cisatracurium
Citalopram
Clindamycin, oral
Clindamycin, parenteral
Clomifene
Clonazepam, parenteral
Clonazepam , oral
Clopidogrel
Clotrimazole, topical
Cloxacillin, parenteral
Coal tar, topical ointment
Coal tar, topical shampoo
Colchicine
Combined oral contraceptive
Conjugated estrogens
Copper IUD
Cotrimoxazole, oral
Cotrimoxazole, parenteral
Cryoprecipitate
Cyanocobalamin (vitamin B12),
parenteral
Cyclopentolate, ophthalmic drops
Cyclopentolate, phenylephrine,
ophthalmic drops
Cyclophosphamide
Cyproterone acetate, oral
Cyproterone acetate, ethinly estradiol
35 mcg
Dantrolene
Dapsone
Desferroxamine (Deferoxamine)
Desmopressin, parenteral
Desmopressin, oral
Desmopressin, nasal spray
Dexamethasone, parenteral
Dexamethasone, oral
Dexamethasone, ophthalmic drops
Dextrose 5%, parenteral
Dextrose 50%, parenteral
Dextrose 10%, parenteral
Dextrose, sodium chloride 0.5/0.9%,
parenteral
7.18, 9.5, 9.16, 10.22, 14.16, 16.6, 17.4,
17.5, 18.3
9.15, 18.2
18.2, 18.7
12.3
15.9, 15.10, 15.11, 15.12, 15.13
3.27, 4.3, 4.5, 4.7, 5.4, 5.9, 8.18, 9.2, 9.3,
10.24, 13.5, 17.6
3.27, 4.3, 4.5, 5.4, 5.9, 9.3, 11.1, 11.4,
13.5, 17.6
5.7
6.10, 14.10, 15.2, 15.3, 15.5, 15.18, 19.23
15.1, 15.12, 15.13
3.4, 3.7
4.13
3.25, 3.26, 4.3, 4.4, 9.3, 13.5
4.11
4.11
13.8
5.1, 5.2, 5.5, 6.4
5.2, 5.15, 15.16
5.14, 6.4
7.17, 10.16, 10.22, 10.23, 10.24, 10.25,
16.13
10.23
2.17
2.4
18.9
18.9
13.11
5.15
4.2
12.9
10.24
19.17
8.27
8.27
8.27
6.16, 6.17, 12.11, 14.17, 14.26
8.4
18.8
2.9, 6.4, 7.11, 8.14, 8.21, 9.13, 10.19,
10.20, 19.6, 19.7, 19.9, 19.14, 19.25, 20.6,
20.8
7.9, 8.2, 8.11, 8.12, 19.21
8.11, 8.12
8.2, 8.14
lxiii
INDEX OF MEDICINES
Diazepam, parenteral
Diazepam, oral
Diclofenac, parenteral
Digoxin, oral
Dinoprost
Dinoprostone, vaginal gel
Dinoprostone, vaginal tablet
Dobutamine
Doxazosin
Doxycycline
Efavirenz
Emtricitabine
Emulsifying ointment BP
Enalapril
Enoxaparin
Ergocalciferol (vitamin D)
Ergometrine
Erythropoietin
Estradiol valerate
Ethambutol
Ethanol
Ethionamide
Etomidate
Factor IX
Factor VIII
Fenoterol, inhalant solution
Fentanyl
Ferrous sulfate Co
Flucloxacillin
Fluconazole, oral
Fluconazole, parenteral
Fludrocortisone
Fluorescein, ophthalmic drops
Fluorescein, ophthalmic strips
Fluoxetine
Flupenthixol
Fluphenazine
Folic acid
Formoterol, inhaler
Fosfomycin
Fresh frozen plasma
Furosemide, oral
Furosemide, parenteral
Ganciclovir
Gentamicin, parenteral
Glibenclamide
6.10, 9.14, 12.9, 12.11, 14.10, 15.2, 15.3,
15.17, 19.16, 19.18, 19.20, 19.22, 19.23,
19.24, 19.28, 19.31, 23.3
15.1, 15.10, 15.12, 15.16, 15.18, 15.19,
15.20, 15.21
7.21, 12.7, 12.8
3.13, 3.14, 3.23
6.23
6.19
6.19
20.6, 20.8
8.28
4.2, 9.9, 9.15
10.2, 10.4, 10.5, 10.11
6.13, 6.14, 10.2, 10.3, 10.4, 10.9, 10.27
4.6
3.6, 3.8, 3.22, 3.30, 3.32, 3.34, 7.4, 8.9
2.8, 2.19, 3.8, 3.23, 6.6, 8.16, 9.15, 14.2
8.23
6.22
7.6
5.15, 5.16
10.11, 10.13, 10.23, 16.18
19.26
16.20, 16.21
12.2, 23.3
2.13
2.13
16.1, 16.9
12.5, 12.12, 23.3, 23.5
2.1, 2.2, 6.1, 7.6
4.3, 4.4, 4.5, 4.6, 9.3, 9.18, 13.5
4.13, 9.3, 10.16, 10.17, 10.19, 10.20,
14.17
10.16
8.3
18.9
18.9
15.8, 15.9, 15.10, 15.11, 15.12, 15.13
15.15
15.15
2.4, 2.6, 2.8, 6.1, 13.2, 14.9
16.9
6.24, 7.15
1.7, 2.14, 2.16, 2.17, 19.30, 20.2
1.9, 3.22, 3.31, 7.5, 7.7, 7.13, 14.14
3.33, 6.7, 7.7, 20.7
10.21, 10.22, 18.8
2.9, 3.25, 3.26, 5.4, 5.9, 6.25, 7.16, 8.18,
9.9, 11.1, 11.4
8.7
lxiv
INDEX OF MEDICINES
Glimepiride
Glucagon
Glycerol 50%
Glyceryl trinitrate, parenteral
Glycopyrrolate
Haemophilus influenza type B
Haloperidol, oral
Haloperidol, parenteral
Halothane
Hepatitis B immunoglobulin
Hepatitis B vaccine
Homatropine,
hydropropylmethylcellulose
Human rabies immunoglobulin
Hydralazine
Hydrochlorothiazide
Hydrocortisone 1%, topical
Hydrocortisone, parenteral
Hydrocortisone, oral
Hydroxypropylmethylcellulose,
ophthalmic drops
Hydroxyurea
Hyoscine butylbromide, parenteral
Hyoscine butylbromide, oral
Ibuprofen
Imipenem
Indomethacin
Influenza vaccine
Insulin, biphasic
Insulin, intermediate acting
Insulin, short acting
Iohexol
Iopamidol
Iopromide
Ioversol
Ipratropium, inhalant solution
Iron, parenteral
Isoflurane
Isoniazid
Isosorbide dinitrate, sublingual
Isosorbide dinitrate, oral
IV fluids
Kanamycin
Ketamine
Labetalol, parenteral
Lactulose
Lamotrigine
8.8
8.11, 8.12
18.6
3.5, 3.6, 3.8, 3.33, 20.7
12.4
11.4
14.5, 14.22, 15.14, 15.18, 23.5
15.2, 15.3, 15.18, 19.23
12.2
1.11, 10.28
1.11, 9.6, 10.28
18.8
9.7, 9.8
6.6
3.22, 3.30, 3.31, 7.7, 14.2
4.6, 4.11
8.2, 8.3, 8.32, 16.2, 16.9, 17.1, 20.1, 20.2
8.2
18.9
2.8, 21.1
12.19
12.19, 15.19
3.34, 4.3, 5.1, 5.2, 5.5, 5.11, 5.12, 6.21,
7.21, 8.24, 8.32, 10.14, 12.5, 12.7, 12.8,
12.16, 13.3, 13.5, 13.6, 13.8, 13.9, 13.10,
13.11, 14.12, 14.15, 14.18, 15.19, 17.4,
17.6, 23.4
2.9, 9.5
6.17
3.21, 9.6, 11.4, 16.6, 16.10
6.3, 8.8, 8.10
6.3, 8.9, 8.10
6.3, 6.4, 8.9, 8.15, 19.21
22.1
22.1
22.1
22.1
16.1, 16.8
2.2, 6.1, 7.6
12.2
10.12, 10.13, 10.15
3.5, 3.8, 3.10, 20.7
3.10, 6.7
6.16, 8.32, 9.14, 20.9, 20.13
16.20
12.2, 12.5, 23.2, 23.3
3.33, 6.8, 12.10
1.8, 1.10, 7.9, 12.18
14.7, 14.8, 14.9, 15.7
lxv
INDEX OF MEDICINES
Lanolin, anhydrous
Lansoprazole, oral
Levodopa, carbidopa
Levofloxacin, oral
Levonorgestrel, oral
Levothyroxine, oral
Lidocaine, parenteral
Lidocaine, pudendal block
Lidocaine, topical jelly
Lidocaine, topical spray
Lidocaine 1%, parenteral
Lidocaine 2%, parenteral
Lidocaine 2% (preservative free)
Lidocaine 1% without adrenaline
(epinephrine), parenteral
Lidocaine with adrenaline
Lidocaine/prilocaine, topical
Lipase
Lipid emulsion, parenteral
Lithium
Loperamide
Lopinavir/ritonavir
Lorazepam, parenteral
Lorazepam, oral
Losartan
Low dose combine contraceptive
Low molecular weight iron dextran
Lugol's Iodine
Lyophilised plasma
Magnesium sulfate
Mannitol 15%, parenteral
Mannitol 25%, parenteral
Mannitol 20%, parenteral
Medroxyprogesterone acetate,
parenteral
Medroxyprogesterone acetate, oral
Meningococcus A,C, bivalent purified
polysaccharides antigen
Meropenem
Metformin
Methadone
Methotrexate, oral
Methyldopa
Methylene blue
Methylprednisolone acetate, parenteral
Metoclopramide, oral
Metoclopramide, parenteral
Metronidazole, oral
Metronidazole, parenteral
18.9
1.2, 1.6, 13.3, 13.6, 13.9
14.21
10.11
5.14, 10.29
8.22
3.19
6.20
12.14
12.14
3.19, 12.14, 19.8
12.14, 19.8
12.14
3.34, 3.35, 5.4, 5.14, 10.30, 13.10
12.14
12.14
1.5
12.9
15.5, 15.6
1.16, 10.20, 15.19
6.13, 10.2, 10.3, 10.5, 10.12, 10.27, 10.28
6.10, 14.10, 15.2, 15.3, 15.5, 15.12, 15.18,
19.23, 23.4, 23.5
12.1, 15.1, 15.21, 23.5
3.22, 7.4
6.4
2.2
8.32
1.7, 1.8, 2.14, 2.16, 2.17, 19.30, 20.2
1.4, 3.19, 6.10, 12.10, 16.2, 19.16
14.26
14.26
18.6
5.1
5.2, 5.5, 5.6, 5.15
11.4
2.9, 9.5
6.3, 8.7
15.19, 15.20
13.1, 13.2
6.8
19.32, 19.33
2.16, 13.4, 13.7
1.11, 6.16, 8.17, 10.30, 12.18, 14.12
1.11, 6.16, 7.21, 12.11, 12.18, 14.12
1.6, 1.14, 1.17, 1.18, 5.4, 5.14, 6.17,
10.30, 14.19
5.4, 9.4, 9.14, 11.1, 11.2, 11.3, 14.9, 17.6
lxvi
INDEX OF MEDICINES
Midazolam, parenteral
Midazolam, oral
Midazolam, buccal
Mifepristone
Misoprostol
Morphine, parenteral
Morphine, oral
Moxifloxacin, parenteral
Moxifloxacin, oral
Naloxone
Natamycin, ophthalmic drops
Neostigmine
Neutral protamine hagedorn
Nevirapine
Nicotinamide
Nifedipine
Nimodipine, oral
Nitrofurantoin
Nitrous oxide
Norethisterone, oral
Ofloxacin, ophthalmic drops
Olanzapine, oral
Omeprazole, oral
Ondansetron, parenteral
Ondansetron, buccal
Orphenadrine
Oxazepam
Oxybuprocaine, ophthalmic drops
Oxybutynin
Oxygen
Oxymetazoline, nasal spray
Oxymetazoline,ophthalmic drops
Oxytocin
Pamidronic acid
Paracetamol, oral
Pethidine
Phenoxymethylpenicillin
Phenylephrine
Phenytoin, parenteral
3.15, 3.17, 3.18, 14.10, 15.2, 19.23, 23.2,
23.4
12.1, 15.1, 15.12
14.10, 15.1, 15.12,
5.12
5.7, 5.8, 5.11, 5.12, 6.20, 6.23
1.4, 3.5, 3.8, 3.20, 5.9, 5.11, 5.13, 6.20,
6.21, 7.21, 9.15, 12.5, 12.6, 12.8, 14.4,
14.12, 14.15, 14.18, 19.4, 20.7, 20.10,
23.3, 23.5
12.16, 12.17
9.4, 16.6, 16.11, 16.13, 16.14, 16.15,
16.20, 16.21
9.4, 10.11, 10.13, 16.6, 16.11, 16.12,
16.13, 16.14, 16.15, 16.20, 16.21
19.15
18.7
12.4
8.8, 8.9
6.13, 6.14, 10.4
14.5
6.8, 6.17
14.4
7.16, 7.17
6.20, 23.2, 23.3
5.2, 5.15
18.3, 18.7
15.7
1.2
6.16, 12.11
12.18
14.21, 15.15
15.23
18.9
7.19
3.4, 3.7, 6.9, 6.20, 10.23, 12.9, 16.1,
16.12, 17.1, 19.31, 19.32, 20.3, 20.4, 20.5,
20.6, 20.7, 20.13
17.2
18.1, 18.2
5.8, 5.9, 6.8, 6.19, 6.22
8.20
4.3, 5.1, 5.11, 5.12, 6.21, 8.16, 9.14, 9.18,
10.14, 12.5, 12.7, 12.8, 12.16, 13.3, 13.5,
13.6, 13.10, 14.4, 14.12, 14.15, 14.18,
15.19, 18.10, 18.11, 19.2, 19.4, 19.8, 19.9,
20.10, 23.4
5.11, 5.13, 6.20, 6.21
3.34, 3.35, 6.15
12.9
14.9, 14.10, 14.11
lxvii
INDEX OF MEDICINES
Phenytoin, oral
Pilocarpine HCL, ophthalmic drops
Piperacillin/tazobactam
Pneumococcal vaccine (23 valent
polysaccharide)
Podophyllin in Tinct. Benz Co
Polyethylene glycol/Sodium sulphate
Polystyrene sulphonate
Polyvalent snake antivenom
Potassium chloride, parenteral
Potassium chloride, oral
Povidone iodine, topical
Praziquantel
Prednisone
Primaquine
Procaine penicillin
Progestin
Promethazine, parenteral
Promethazine, oral
Propofol
Propranolol
Pyrazinamide
Pyridostigmine
Pyridoxine
Quinine, parenteral
Rabies vaccine
Radioactive iodine
Rifabutin
Rifampicin
Rifampicin, isoniazid
Rifampicin, isoniazid, pyrazinamide,
ethambutol
Ringer Lactate
Risperidone, oral
Rocuronium
Salbutamol, parenteral
Salbutamol, inhalant solution
Salbutamol, inhaler
Salmeterol/fluticascone, inhaler
Scorpion antivenom
Selenium sulphide
Sennosides A and B
Sevoflurane
Silver sulfadiazine
Simvastatin
Sodium bicarbonate, parenteral
14.7, 14.11
18.5
2.9, 9.4
2.8, 9.6, 11.4
4.14
1.1
7.9
19.5
6.4, 7.10, 8.14, 19.18, 19.20
7.10
4.10
7.14
1.7, 2.6, 2.15, 4.6, 8.2, 8.21, 8.32, 10.15,
10.23, 13.2, 13.8, 13.11, 14.13, 14.17,
14.20, 14.24, 16.1, 16.2, 16.4, 16.9, 16.10,
16.13, 17.2
10.24
6.15
5.2, 5.6, 6.4
12.11, 14.22, 15.2
12.18, 17.7
12.2, 14.11, 23.2, 23.3, 23.4
14.22, 15.15
10.12, 10.13, 16.19, 16.20, 16.21
14.25
6.16, 10.15, 14.23, 16.17, 16.20, 19.20,
19.26
9.13
9.7, 9.8
8.30, 8.31
10.5
3.25, 9.9, 10.12, 14.16, 16.18
16.17
16.17
12.8
15.5, 15.14
12.4
6.18
7.9, 16.1, 16.8, 16.9, 20.3
16.1, 16.4, 16.9, 16.10
16.4, 16.10
19.7
4.13
12.18
12.2
20.10
3.3, 3.6, 3.8, 3.10, 3.11, 3.31, 8.9, 8.19,
14.2, 14.3
19.16, 19.27
lxviii
INDEX OF MEDICINES
Sodium chloride 0.9%, parenteral
Sodium chloride 0.9%, irrigation solution
Sodium chloride 0.45%, parenteral
Sodium chloride 5%, parenteral
Sodium citrate, solution
Sodium cromoglycate, ophthalmic drops
Sodium hyaluronate, ophthalmic
injection
Sodium phosphate, enema
Solutions for parenteral nutrition,
combinations
Spider antivenom
Spironolactone
Sterile intraocular irrigating solution
Sterile water
Streptokinase
Sulfasalazine
Suxamethonium
Tamoxifen
Tamsulosin
Tenofovir
Tenofovir/emtricitabine/efavirenz
Tenofovir/emtricitabine/lopinavir/
ritonavir
Tenofovir/emtricitabine/nevirapine
Terizidone
Testosterone cypionate
Tetanus immunoglobulin
Tetanus toxoid
Tetracaine, ophthalmic drops
Theophylline
Thiamine (vitamin B1), oral
Thiamine (vitamin B1), parenteral
Thiopental
Timolol, ophthalmic drops
Tramadol, oral
Tramadol, parenteral
Tranexamic acid, oral
Tranexamic acid, parenteral
Tretinoin, topical
Tropicamide, ophthalmic drops
Unfractionated heparin
Valganciclovir
Valproate, oral
1.4, 2.2, 3.4, 3.16, 5.8, 5.9, 5.13, 6.1, 6.8,
6.10, 6.17, 6.18, 6.19, 6.21, 6.22, 6.24,
7.9, 7.10, 7.13, 8.2, 8.13, 8.14, 8.15, 8.20,
9.8, 12.8, 14.9, 14.10, 16.1, 16.2, 16.8,
17.1, 18.1, 18.10, 19.5, 19.6, 19.7, 19.9,
19.20, 19.21, 19.30, 20.2, 20.3, 20.4, 20.5,
20.6, 20.8, 20.10, 20.13
4.10, 18.11, 20.13
7.10, 8.14
7.13
12.12
18.2
18.9
7.9
12.19
19.9
1.9, 3.22, 3.23, 3.31, 8.29
18.9
4.10, 18.1, 20.13
3.4
13.1, 13.2
12.2, 12.3
21.1
7.19
1.12, 6.13, 6.14, 10.4, 10.27
6.12, 6.13, 10.2, 10.17, 10.20, 18.8
10.2, 10.3
10.2
16.20, 16.21
7.20, 8.4, 8.26
9.14, 19.3, 19.8, 19.9
9.6, 9.8, 9.14, 19.3, 19.7, 19.9, 20.10
18.10
16.10
1.7, 3.24, 14.6, 15.16, 15.18, 19.26
3.24, 14.6, 15.18, 19.25
12.2, 14.11
18.4, 18.5
9.18, 12.5, 12.7, 12.16, 15.19, 15.20
7.21, 12.6
2.13, 2.14, 5.2
6.23, 20.3
4.2
18.9
2.18, 2.19, 2.8, 3.23, 3.8, 6.6, 8.15, 9.15,
14.2
10.21, 10.22, 18.8
14.7, 14.8, 15.5, 15.6
lxix
INDEX OF MEDICINES
Vancomycin, oral
Vancomycin, parenteral
Vancomycin, intravitreal
Varicella-zoster immunoglobulin
Vecuronium
Verapamil, oral
Vincristine
Vitamin B complex, parenteral
Vitamin B complex, oral
Vitamin K1 (Phytomenadione), oral
Vitamin K1 (Phytomenadione),
parenteral
Warfarin
Water for injection
Zidovudine
Zidovudine/lamivudine
Zidovudine/lamivudine/lopinavir/
ritonavir
Zidovudine/lamivudine/lopinavir/ritonavir
/tenofovir
Zuclopenthixol
1.17
2.9, 3.24, 3.25, 3.26, 9.3, 9.4, 14.16
18.3
9.17
12.3
3.13, 3.14, 3.16, 14.13
21.1
6.16
14.6
19.30, 19.31
19.30
2.19, 3.13, 3.23, 6.6, 14.3
3.34, 3.35
6.12, 10.2, 10.4
10.27, 10.3
10.3
10.3
15.2, 15.15
lxx
ABBREVIATIONS
3TC
ab
ABC
ACE-inhibitor
ABG analysis
ACR
ACTH
ADR
AED
AIDP
AIDS
AKI
ALP
ALT
ANCA
ANF
anti-HBs
anti-Hbe
aPTT
ARB
ARDS
ART
ARV
AST
ATV/r
AV
AZT
BCG vaccine
Beta-HCG test
BMI
BMD
BP
0
C
Ca
CAB
CAD
CCF
CD
CD4
CIDP
CIN
CK
CKD
Cl
CLAT
cm
cmv
CNS
CO2
COPD
CPAP
CPR
CrAg
CrCl
CRP
CSF
CSU
CT
lamivudine
antibody
abacavir
angiotensin-converting-enzyme inhibitor
arterial blood gas analysis
albumin/creatinine ratio
adrenocorticotropic hormone
adverse drug reaction
automated external defribillator
acute inflammatory demyelinating polyradiculoneuropathy
Acquired Immune Deficiency Syndrome
acute kidney injury
alkaline phosphatase
alanine transaminase
antineutrophil cytoplasmic antibodies
antinuclear factor
antibody to the hepatitis B surface antigen
hepatitis B e-antibody
activated partial thromboplastin time
angiotensin II receptor blocker
acute respiratory distress syndrome
antiretroviral therapy
antiretroviral medicine
aspartate aminotransferase
atazanavir/ritonavir
atrioventricular
zidovudine
Bacillus Calmette–Guérin vaccine
beta-human chorionic gonadotropin test
body mass index
bone mineral density
blood pressure
(degrees) Celcius
calcium
circulation airways breathing
coronary artery disease
congestive cardiac failure
Crohn’s disease
cluster of differentiation 4
chronic inflammatory demyelinating polyradiculoneuropathy
contrast induced nephrotoxicity
creatinine kinase
chronic kidney disease
chloride
cryptococcus latex agglutination test
centimetre
cytomegalovirus
central nervous system
carbon dioxide
chronic obstructive pulmonary disease
continuous positive airway pressure
cardiopulmonary resuscitation
cryptococcal antigen
creatinine clearance
C-reactive protein
cerobrospinal fluid
catheter specimen urine
computerized tomography
lxxi
ABBREVIATIONS
CVA
CVD
CVS
CXR
d4T
DBP
DC
DIC
DILI
DKA
dL
DMARD
DMPA
DNA
DRESS
DR-TB
DU
DVT
E or EMB
ECG
EEG
EFV
eGFR
ELISA
EML
EPI
ESR
ESRD
FBC
FDC
FEV1
FFP
FH
FiO2
FPG
FSH
FTA-abs
FTC
FVC
G6PD
g
GDM
GGT
GH
GI(T)
GORD
GU
H or INH
HAP
Hb
HbA1c
HbeAg
HBIG
HbS
HBsAb
HBsAg
HbSS
HBV
HCl
cerebral vascular accident
cardiovascular disease
cardiovascular system
chest X-ray
stavudine
diastolic blood pressure
direct current
disseminated intravascular coagulation
drug-induced liver injury
hyperglycaemia diabetic ketoacidosis
decilitre
disease-modifying antirheumatic drug
depot medroxyprogesterone acetate
deoxyribonucleic acid
drug reaction with eosinophilia and systemic symptoms
drug resistant tuberculosis
duodenal ulcer
deep venous thrombosis
ethambutol
electrocardiogram
electroencephalogram
efavirenz
estimated glomerular filtration rate
enzyme-linked immunosorbent assay
essential medicine list
expanded programme on immunisation
erythrocyte sedimentation rate
end stage renal disease
full blood count
fixed dose combination
forced expiratory volume in 1 second
fresh frozen plasma
familial hypercholesterolaemia
fraction of inspired oxygen
fasting plasma glucose
follicle-stimulating hormone
fluorescent treponemal antibody absorption
emtricitabine
forced vital capacity
glucose-6-phosphate dehydrogenase
gram
gestational diabetes
gamma-glutamyl transferase
growth hormone
gastrointestinal (tract)
gastro-oesophageal reflux disease
gastrointestinal ulcer
isoniazid
hospital-acquired pneumonia
haemoglobin
glycosylated haemoglobin
hepatitis B e-antigen
hepatitis B immune globulin
sickle haemoglobin
hepatitis B surface antibody
hepatitis B surface antigen
sickle cell haemoglobin
hepatitis B virus
hydrochloric acid
lxxii
ABBREVIATIONS
HCO3
HCW
HCV
HDL
Hep B
HHS
HIV
HMGCoA
H2O
HR
HRIG
HSV
HT
ICS
ICU
IgG
IgM
IM
INR
IOP
IPT
IRIS
ITP
IU
IUD
IV
J
K+
kg
KS
L
LABA
LBBB
LDH
LDL (-C)
LH
LoE
LMWH
LP
LPA
LPV/r
LV
MAC
mcg
MCH
MCV
MDEA
MDI
MDR-TB
MDMA
mg
MI
min
mL
mm3
mmHg
mmoL
mOsm
MRI
bicarbonate
healthcare workers
hepatitis C virus
high-density lipoprotein
hepatitis B
hyperosmolar hyperglycaemic state
human immunodeficiency virus
3-hydroxy-3-methylglutaryl–coenzyme A
water
heart rate
human rabies immunoglobulin
herpex simplex virus
hormone therapy
Inhaled corticosteroid
Intensive care unit
immunoglobulin G
immunoglobulin M
intramuscular
international normalized ratio
intraocular pressure
isoniazid preventive therapy
immune reconstitution inflammatory syndrome
immune thrombocytopenia
international unit
intrauterine contraceptive device
intravenous
Joule
potassium
kilogram
Kaposi Sarcoma
litre
long-acting beta2 agonist
left bundle branch block
lactate dehydrogenase
low-density lipoprotein (-cholesterol)
luteinizing hormone
level of evidence
low molecular weight heparin
lumbar puncture
line probe assay
lopinavir/ritonavir
left ventricular
minimum alveolar concentration
microgram
mean corpuscular haemoglobin
mean corpuscular volume
3,4-methylenedioxy-N-ethylamphetamine (“Ice”, “Eve”)
metered dose inhaler
multi-drug resistant tuberculosis
3,4-methylenedioxymethamphetamine (“Ecstacy”)
milligram
myocardial infarction
minute
millilitre
Cubic millimetre
Millimeters mercury
millimole
milliosmole
magnetic resonance imaging
lxxiii
ABBREVIATIONS
MRSA
MSU
MTB
MU
MVA
Na
NaCl
NEMLC
NAC
NERD
NICD
NICE
NMA
nmol
NNRTI
NPH insulin
NRS
NRTI
NSAID
NSTEMI
NVP
NYHA
ORS
PaCO2
PaO2
PAIR
PCA device
PCR
PEF
PEG
PEP
pH
PHC
PI
PID
PMTCT
PO4
PONV
PPG
PPH
PPI
PPROM
PROM
PT
PTH
PTL
PTT
PV
PZA or Z
RA
R or RIF
RBC
Rh
RH
RHZE
RNA
RF
RPR
RRT
Methicillin (cloxacillin) resistant S. aureus
midstream specimen of urine
Mycobacterium tuberculosis
million units
manual vacuum aspiration
sodium
sodium chloride
National Essential Medicines List Committee
N-acetylcysteine
non-erosive reflux disease
National Institute for Communicable Diseases
National Institute for Health and Care Excellence
normetanephrine
nanomole
non-nucleoside reverse transcriptase inhibitor
Neutral Protamine Hagedorn insulin
numeric rating scale
nucleoside reverse transcriptase inhibitor
non steroidal anti-inflammatory drug
non ST elevation myocardial infarction
nevirapine
New York Heart Association (functional classification)
oral rehydration solution
partial pressure of carbon dioxide in arterial blood
partial pressure of oxygen in arterial blood
percutaneous aspiration injection of helminthicidal agent and re-aspiration
patient controlled analgesia device
polymerase chain reaction
peak expiratory flow
polyethylene glycol
post exposure prophylaxis
acidity (partial pressure of hydrogen)
primary healthcare
protease inhibitor
pelvic inflammatory disease
prevention of mother to child transmission
phosphate
post operative nausea and vomiting
post prandial plasma glucose
post-partum haemorrhage
proton pump inhibitor
preterm prelabour rupture of membranes
prelabour rupture of membranes at term
prothrombin time
parathyroid hormone
preterm labour
partial thromboplastin time
per vagina (vaginal route)
pyrazinamide
rheumatoid arthritis
rifampicin
red blood cell
Rhesus
rifampicin/isoniazid combination
rifampicin/isoniazid/pyrazinamide/ethambutol combination
ribonucleic acid
rheumatoid factor
rapid plasma reagin
renal replacement therapy
lxxiv
ABBREVIATIONS
RUT
SABA
SBGM
SBP
SC
SJS
SIADH
SL
SLE
SSRI
STEMI
STG
STI
T3
T4
TB
TB-IRIS
TBSA
TCA
TDD
TDF
TEN
TIA
TOP
TP
TPHA
TPN
TSH
TST
TTP HUS
UA
UDV
UE
UEA
ULN
UTI
VDRL test
VF
VHF
VL
VMA
VSD
VT
VTE
VZIG
VWF
WCC
WHO
WPW syndrome
XDR-TB
rapid urine test
short-acting beta2 agonist
self-blood glucose monitoring
systolic blood pressure
subcutaneously
Stevens-Johnson syndrome
syndrome of inappropriate antidiuretic hormone
sublingual
systemic lupus erythematosus
selective serotonin re-uptake inhibitor
ST elevation myocardial infarction
standard treatment guideline
sexually transmitted infection
triiodothyronine
thyroxine
tuberculosis
TB immune reconstitution inflammatory syndrome
total body surface area
tricyclic antidepressants
total daily dose
tenofovir
toxic epidermal necrolysis
transient ischaemic attack
termination of pregnancy
Treponema pallidum
Treponema pallidum haemagglutination assay
total parenteral nutrition
thyroid-stimulating hormone
tuberculin skin test
thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome
unstable angina
unit dose vial
ung. emulsificans BP (emulsifying ointment)
ung. emulisificans aqueosum BP (aqueous cream)
upper limit of normal
urinary tract infection
venereal disease research laboratory test
ventricular fibrillation
viral haemorrhagic fever
viral load
vanillylmandelic acid
ventricular septal defect
ventricular tachycardia
venous thromboembolism
varicella-zoster immunoglobulin
von Willebrand factor
white cell count
World Health Organisation
Wolff-Parkinson-White syndrome
extensively drug-resistant tuberculosis
lxxv
PEAK EXPIRATORY FLOW RATES
Peak expiratory flow in normal adult subjects
Adapted with permission from
Nunn AJ Gregg I, Br Med J 1989:298;1068-70
and Clement Clarke International.
lxxvi
CALCULATING % PREDICTED PEAK FLOW RATE




Take the best of 3 of the patient’s observed peak flow rate:
e.g. 200, 180, 190 performed – so take 200.
Find the patient’s sex, age and height predicted value from the nomogram.
e.g. 440 for a woman of age 25 years and height 167 cm
Divide patient’s observed peak flow rate over their predicted peak flow rate:
e.g. 200/440 = 0.45
Multiply by 100:
e.g. 0.45X100 = 45%
So, in this example, the patient’s observed peak flow rate is 45% of predicted.
CALCULATING PEAK FLOW VARIABILITY
There are a number of methods for calculating PEF variability.
One method is described below:

Subtract the lowest from the highest reading.

Divide by the highest reading.

Multiply by 100.
So, in this example, where a patient has readings of 300 to 400, the variability is
25%. If these readings were taken before and after a test dose of salbutamol,
asthma is diagnosed. (See sections 16.1 Asthma, acute and 16.2 Asthma,
chronic persistent).
lxxvii
ASTHMA CONTROL TEST®
This is a validated measure of clinical asthma control that can be completed by
the patient (after initial instruction) at each visit to the clinic prior to
consultation. A value of ≥19 suggests adequate asthma control.
SCORE
1. During the past 4 weeks, how often have you had shortness of breath?
1: Not at all
2: Once or twice
a week
3: 3 to 6 times a
week
4: Once a day
5: More than once a
day
2. Rate your asthma control during the past 4 weeks?
1:Not controlled
at all
2: Poorly
controlled
3: Somewhat
controlled
4: Well
controlled
5: Completely
controlled
3. During the past 4 weeks, how often have you used your rescue inhaler or
nebulizer medication?
1: None of the
time
2: A little of the
time
3: Some of the
time
4: Most of the
time
5: All the time
4. During the past 4 weeks, has asthma keep you from getting as much done at
work or home?
1: Not at all
2: Once a week
or less
3: A few times a
week
4: 1 or 2 times
per day
5: 3 or more times
a day
5. During the past 4 weeks, has asthma symptoms woken you up at night or
earlier than usual?
1: Not at all
2: Once or twice
3: Once a week
4: 2 to 3 nights
a week
5: 4 or more nights a
week
A total score of ≥19 suggests adequate asthma control.
Sourced from: Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus
P, Murray JJ, Pendergraft TB. Development of the asthma control test: a
survey for assessing asthma control. J Allergy Clin Immunol. 2004
Jan;113(1):59-65. http://www.ncbi.nlm.nih.gov/pubmed/14713908
lxxviii
USEFUL NUMBERS AND URL LINKS
POISONS INFORMATION CENTRES
Poison Information Helpine of the Western Cape
Red Cross War Memorial Children’s Hospital Poisons
Information Service
Tygerberg Poison Information Centre
University of the Free State Poison Control and
Medicine Information Centre
0861555 777
0861555 777
0861555 777
www.sun.ac.za/poisoncentre
082491 0160
Information on poisons
https://www.afritox.co.za/
COMMUNICABLE DISEASES
Rabies hotline (NICD)
082883 9920
Viral Haemmorhagic Fever outbreak hotline (NICD)
082883 9920
South African Vaccine Producers
0113866063/2/00
MEDICINE INFORMATION CENTRES
Medicine Information Centre (Cape Town)
0214066829
0861100531
Amayeza Info Centre
011678 2332
National HIV Healthcare Worker Hotline
0800 212 506
0214066782
DEPARTMENT OF HEALTH
National Department Health website
www.health.gov.za
Essential Drugs Programme
www.health.gov.za/edp.php
[email protected]
Third line ART applications
[email protected]
Medicine stock availability reporting
[email protected]
The National Adverse Drug Event Monitoring Centre
(NADEMC)
021 4471618
Fax: 021448 6181
MISCELLANEOUS
Ideal weight calculator
http://www.calculator.net/ideal-weightcalculator.html#
List of local haemophilia centres
http://www.haemophilia.org.za/centres.html
Medicines causing QT prolongation
www.sads.org.uk/drugs_to_avoid.htm
eGFR calculator
https://www.kidney.org/professionals/KDOQ
I/gfr_calculator
Medicines requiring dose adjustment in renal
impairment
Dietary phosphate restriction
http://www.globalrph.com/index_renal.htm
Water deficit calculator
http://www.nephromatic.com/water_deficit.p
hp
https://unckidneycenter.org/files/kidneyhealth-library-files/renaldiet_phosphorus.pdf
TIMI: http://www.mdcalc.com/timi-riskscore-for-uanstemi/
Grace Risk Scores:
http://www.mdcalc.com/grace-acs-risk-andmortality-calculator/
Risk stratification calculators in NSTEMI
lxxix